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Saturday, November 14, 2020

Arctic exploration

From Wikipedia, the free encyclopedia

The Arctic region is within the red line

Arctic exploration is the physical exploration of the Arctic region of the Earth. It refers to the historical period during which mankind has explored the region north of the Arctic Circle. Historical records suggest that humankind have explored the northern extremes since 325 BC, when the ancient Greek sailor Pytheas reached a frozen sea while attempting to find a source of the metal tin. Dangerous oceans and poor weather conditions often fetter explorers attempting to reach polar regions and journeying through these perils by sight, boat, and foot has proven difficult.

Ancient Greece

Some scholars believe that the first attempts to penetrate the Arctic Circle can be traced to ancient Greece and the sailor Pytheas, a contemporary of Aristotle and Alexander the Great, who, in 325 BC, attempted to find the source of the tin that would sporadically reach the Greek colony of Massilia (now Marseille) on the Mediterranean coast. Sailing past the Pillars of Hercules, he reached Brittany and then Cornwall, eventually circumnavigating the British Isles. From the local population, he heard news of the mysterious land of Thule, even farther to the north. After six days of sailing, he reached land at the edge of a frozen sea (described by him as "curdled"), and described what is believed to be the aurora and the midnight sun. Some historians claim that this new land of Thule was either the Norwegian coast or the Shetland Islands based on his descriptions and the trade routes of early British sailors. While no one knows exactly how far Pytheas sailed, he may have crossed the Arctic Circle. Nevertheless, his tales were regarded as fantasy by later Greek and Roman authorities, such as the geographer Strabo.

The Middle Ages

Viking sailors reached the White Sea and Greenland and North America

The first Viking to sight Iceland was Gardar Svavarsson, who lost his route due to harsh conditions when sailing from Norway to the Faroe Islands. This quickly led to a wave of colonization. Not all the settlers were successful however in the attempts to reach the island. In the 10th century, Gunnbjörn Ulfsson got lost in a storm and ended up within sight of the Greenland coast. His report spurred Erik the Red, an outlawed chieftain, to establish a settlement there in 985. While they flourished initially, these settlements eventually foundered due to changing climatic conditions (see Little Ice Age).They are believed to have survived until around 1450.

Greenland's early settlers sailed westward, in search of better pasturage and hunting grounds. Modern scholars debate the precise location of the new lands of Vinland, Markland, and Helluland that they discovered.

The Scandinavian peoples also pushed farther north into their own peninsula by land and by sea. As early as 880, the Viking Ohthere of Hålogaland rounded the Scandinavian Peninsula and sailed to the Kola Peninsula and the White Sea. The Pechenga Monastery on the north of Kola Peninsula was founded by Russian monks in 1533; from their base at Kola, the Pomors explored the Barents Region, Spitsbergen, and Novaya Zemlya—all of which are in the Arctic Circle. They also explored north by boat, discovering the Northern Sea Route, as well as penetrating to the trans-Ural areas of northern Siberia. They then founded the settlement of Mangazeya east of the Yamal Peninsula in the early 16th century. In 1648 the Cossack Semyon Dezhnyov opened the now famous Bering Strait between America and Asia.

Russian settlers and traders on the coasts of the White Sea, the Pomors, had been exploring parts of the northeast passage as early as the 11th century. By the 17th century they established a continuous sea route from Arkhangelsk as far east as the mouth of Yenisey. This route, known as Mangazeya seaway, after its eastern terminus, the trade depot of Mangazeya, was an early precursor to the Northern Sea Route.

Age of Discovery

Mercator's map of the North Pole (1606)

Exploration to the north of the Arctic Circle in the Renaissance was both driven by the rediscovery of the Classics and the national quests for commercial expansion, and hampered by limits in maritime technology, lack of stable food supplies, and insufficient insulation for the crew against extreme cold.

Renaissance advancements in cartography

Patent from King Henry VII, authorizing John Cabot and his sons to explore new lands in the west

A seminal event in Arctic exploration occurred in 1409, when Ptolemy's Geographia was translated into Latin, thereby introducing the concepts of latitude and longitude into Western Europe. Navigators were better able to chart their positions, and the European race to China, sparked by interest in the writings of Marco Polo, commenced. The Inventio Fortunata, a lost book, describes in a summary written by Jacobus Cnoyen but only found in a letter from Gerardus Mercator, voyages as far as the North Pole. One widely disputed claim is that two brothers from Venice, Niccolo and Antonio Zeno, allegedly made a map of their journeys to that region, which were published by their descendants in 1558.

Northwest Passage

The Northwest Passage connects the Atlantic and Pacific Oceans via the Arctic Ocean. Since the discovery of the American continent was the product of the search for a route to Asia, exploration around the northern edge of North America continued for the Northwest Passage. John Cabot's initial failure in 1497 to find a Northwest Passage across the Atlantic led the British to seek an alternative route to the east.

Interest re-kindled in 1564 after Jacques Cartier's discovery of the mouth of the Saint Lawrence River. Martin Frobisher had formed a resolution to undertake the challenge of forging a trade route from England westward to India. From 1576 to 1578, he took three trips to what is now the Canadian Arctic in order to find the passage. Frobisher Bay is named after him. In July 1583, Sir Humphrey Gilbert, who had written a treatise on the discovery of the passage and was a backer of Frobisher's, claimed the territory of Newfoundland for the English crown.

In 1585, under the employ of Elizabeth I, the English explorer John Davis entered Cumberland Sound, Baffin Island. Davis rounded Greenland before dividing his four ships into separate expeditions to search for a passage westward. Though he was unable to pass through the icy Arctic waters, he reported to his sponsors that the passage they sought is "a matter nothing doubtfull [sic]," and secured support for two additional expeditions, reaching as far as Hudson Bay.

Though England's efforts were interrupted in 1587 because of the Anglo-Spanish War, Davis's favorable reports on the region and its people would inspire explorers in the coming century. In 1609, while in the service of the Dutch East India Company, the English explorer Henry Hudson sailed up what is now called the Hudson River in search of the Passage; he reached present-day Albany, New York, before giving up. He later explored further north into the Arctic and Hudson Bay for the Passage.

The Northeast Passage

Jan Jansson's map of the "Poli Arctici" from 1644.

The Northeast Passage is a broad term for any route lying above the Eurasian continent and stretching between the waters north of the Norwegian Sea to the Bering Strait. The "Northern Sea Route" is defined as a specific portion of such routes. The Northern Sea Route (capitalized) as currently officially defined by Russian Federation law includes shipping lanes falling within Russia's EEZ and extending from the Kara Sea to the Bering Strait along the Russian northern coast.

The idea to explore this region was initially economic, and was first put forward by Russian diplomat Dmitry Gerasimov in 1525. The entire route lies in Arctic waters and parts are only totally free of ice for about two months per year, making it a very perilous journey.

In the mid-16th century, John Cabot's son Sebastian helped organize just such an expedition, led by Sir Hugh Willoughby and Richard Chancellor. Willoughby's crew was shipwrecked off the Kola Peninsula, where they eventually died of scurvy. Chancellor and his crew made it to the mouth of the Dvina River and the town of Arkhangelsk, where they were met by a delegation from the Tsar, Ivan the Terrible. Brought back to Moscow, he launched the Muscovy Company, promoting trade between England and Russia. This diplomatic course allowed British Ambassadors such as Sir Francis Cherry the opportunity to consolidate geographic information developed by Russian merchants into maps for British exploration of the region. Some years later, Steven Borough, the master of Chancellor's ship, made it as far as the Kara Sea, when he was forced to turn back because of icy conditions.

Spitsbergen and Svalbard during the Golden Age of Dutch exploration and discovery (ca. 1590s–1720s). Portion of 1599 map of Arctic exploration by Willem Barentsz. Spitsbergen, here mapped for the first time, is indicated as "Het Nieuwe Land" (Dutch for "the New Land"), center-left. This is a typical map from the Golden Age of Netherlandish cartography.
 
A Dutch map of Jan Mayen during the Golden Age of Dutch exploration and discovery (ca. 1590s–1720s). The Dutch were the first to undisputedly explore and chart coastlines of Jan Mayen and the Svalbard archipelago in the Arctic Ocean.

Western parts of the passage were simultaneously being explored by Northern European countries like England, the Netherlands, Denmark and Norway, looking for an alternative seaway to China and India. Although these expeditions failed, new coasts and islands were discovered. Most notable is the 1596 expedition led by Dutch navigator Willem Barentsz who discovered Spitsbergen and Bear Island.

Fearing English and Dutch penetration into Siberia, Russia closed the Mangazeya seaway in 1619. Pomor activity in Northern Asia declined and the bulk of exploration in the 17th century was carried out by Siberian Cossacks, sailing from one river mouth to another in their Arctic-worthy kochs. In 1648 the most famous of these expeditions, led by Fedot Alekseev and Semyon Dezhnev, sailed east from the mouth of Kolyma to the Pacific and doubled the Chukchi Peninsula, thus proving that there was no land connection between Asia and North America. Eighty years after Dezhnev, in 1728, another Russian explorer, Danish-born Vitus Bering on Sviatoy Gavriil made a similar voyage in reverse, starting in Kamchatka and going north to the passage that now bears his name (Bering Strait). It was Bering who gave their current names to Diomede Islands, discovered and first described by Dezhnev.

It was not until in 1878 that Finnish-Swedish explorer Adolf Erik Nordenskiöld made the first complete passage of the North East Passage from west to east, in the Vega expedition. The ship's captain on this expedition was Lieutenant Louis Palander of the Swedish Royal Navy.

Northwest Passage

Sailing Ship in Arctic Regions
 
Roald Amundsen led the first expedition to reach the South Pole, was the first person to reach both poles, and was the first person to traverse the Northwest Passage.

In the first half of the 19th century, parts of the Northwest Passage were explored separately by a number of different expeditions, including those by John Ross, William Edward Parry, James Clark Ross; and overland expeditions led by John Franklin, George Back, Peter Warren Dease, Thomas Simpson, and John Rae. Sir Robert McClure was credited with the discovery of the Northwest Passage by sea in 1851 when he looked across M'Clure Strait from Banks Island and viewed Melville Island. However, the strait was blocked by young ice at this point in the season, and not navigable to ships. The only usable route, linking the entrances of Lancaster Sound and Dolphin and Union Strait was first used by John Rae in 1851. Rae used a pragmatic approach of traveling by land on foot and dog sled, and typically employed less than ten people in his exploration parties.

The Northwest Passage was not completely conquered by sea until 1906, when the Norwegian explorer Roald Amundsen, who had sailed just in time to escape creditors seeking to stop the expedition, completed a three-year voyage in the converted 47-ton herring boat Gjøa. At the end of this trip, he walked into the city of Eagle, Alaska, and sent a telegram announcing his success. His route was not commercially practical; in addition to the time taken, some of the waterways were extremely shallow.

Knud Rasmussen (1879 - 1933) led several Arctic expeditions. He grew up in Greenland speaking Greenlandic and Danish, and has been called the "father of Eskimology" and was the first Greenlander of Inuit and European descent to cross the Northwest Passage via dog sled. Rasmussen and his friend Peter Freuchen participated in seven Thule Expeditions, named after ultima Thule, and wrote numerous books on their Arctic experiences.

The North Pole

Robert Peary and sledge party with flags at North Pole. Peary has been claimed to be the first person to reach the North Pole.

On April 6, 1909, Robert Peary claimed to be the first person in recorded history to reach the North Pole (although whether he actually reached the Pole is disputed). He traveled with the aid of dogsleds and three separate support crews who turned back at successive intervals before reaching the Pole. Many modern explorers, including Olympic skiers using modern equipment, contend that Peary could not have reached the pole on foot in the time he claimed.

A number of previous expeditions set out with the intention of reaching the North Pole but did not succeed; that of British naval officer William Edward Parry in 1827, the tragic American Polaris expedition under Charles Francis Hall in 1871, the ill-fated Jeannette Expedition commanded by US Navy Lieutenant Commander George W. De Long in 1879, and the Norwegian Fram expedition of Fridtjof Nansen in 1895. American Frederick Cook claimed to have reached the North Pole in 1908, but this has not been widely accepted.

On May 9, 1926, Americans Richard E. Byrd and Floyd Bennett claimed to have flown over the North Pole in a Fokker F.VIIa/3m Tri-motor monoplane. However, their claim to have reached the Pole is disputed.

The crew of the airship Norge (including Roald Amundsen and the American sponsor Lincoln Ellsworth) flew over the Pole on May 12, 1926. This is the first undisputed sighting of the Pole. Norge was designed and piloted by the Italian Umberto Nobile, who overflew the Pole a second time on May 24, 1928. Nobile’s second trip was in the airship Italia that ran into a storm on the return trip and crashed on the ice. Survivors were eventually recovered. Amundsen disappeared, with the crew of his sea plane, during the rescue operations.

The first people to have without doubt walked on the North Pole were the Soviet party of 1948 under the command of Alexander Kuznetsov, who landed their aircraft nearby and walked to the pole.

On August 3, 1958, the American submarine USS Nautilus (SSN-571) reached the North Pole without surfacing. It then proceeded to travel under the entire Polar ice cap. On March 17, 1959, the USS Skate (SSN-578) surfaced on the North Pole and dispersed the ashes of explorer Sir Hubert Wilkins. These journeys were part of military explorations stimulated by the Cold War context.

On April 19, 1968, Ralph Plaisted reached the North Pole via snowmobile, the first surface traveler known with certainty to have done so. His position was verified independently by a US Air Force meteorological overflight. In 1969 Wally Herbert, on foot and by dog sled, became the first man to reach the North Pole on muscle power alone, on the 60th anniversary of Robert Peary's famous but disputed expedition.

The first persons to reach the North Pole on foot (or skis) and return with no outside help, no dogs, air planes, or re-supplies were Richard Weber (Canada) and Misha Malakhov (Russia) in 1995. No one has completed this journey since.

U.S. Air Force Lieutenant Colonel Joseph O. Fletcher and Lieutenant William Pershing Benedict landed a plane at the Pole on May 3, 1952, accompanied by the scientist Albert P. Crary.

On 2 May 2007, BBC's Top Gear got to the 1996 position of the magnetic north pole (78°35.7′N 104°11.9′W) in modified Toyota Hilux.

On 2 August 2007, during Arktika 2007 Russian manned submersibles were the first to descend to the sea-bed below the pole.

On April 26, 2009, Vassily Elagin, Afanassi Makovnev, Vladimir Obikhod, Sergey Larin, Alexey Ushakov, Alexey Shkrabkin and Nikolay Nikulshin after 38 days and over 2,000 km (1,200 mi) (starting from Sredniy Island, Severnaya Zemlya) drove two Russian built cars "Yemelya-1" and "Yemelya-2" to the North Pole.

Corinth Canal

From Wikipedia, the free encyclopedia

Coordinates: 37°56′05″N 22°59′02″E

Corinth Canal
Canal of Corinth.jpg
Specifications
Length6.4 km (4.0 miles)
Maximum boat beam17.6 m (58 ft)
Maximum boat draft7.3 m (24 ft)
Locks0
StatusOpen
History
Principal engineerIstván Türr and Béla Gerster
Construction began1881
Date of first use25 July 1893

The Corinth Canal (Greek: Διώρυγα της Κορίνθου, romanizedDhioryga tis Korinthou) connects the Gulf of Corinth in the Ionian Sea with the Saronic Gulf in the Aegean Sea. It cuts through the narrow Isthmus of Corinth and separates the Peloponnese from the Greek mainland, arguably making the peninsula an island. The canal was dug through the isthmus at sea level and has no locks. It is 6.4 kilometres (4 mi) in length and only 21.4 metres (70 ft) wide at its base, making it impassable for many modern ships. It has little economic importance and is mainly a tourist attraction.

The canal was initially proposed in classical times and a failed effort was made to build it in the 1st century AD. Construction recommenced in 1881 but was hampered by geological and financial problems that bankrupted the original builders. It was completed in 1893, but, due to the canal's narrowness, navigational problems, and periodic closures to repair landslides from its steep walls, it failed to attract the level of traffic expected by its operators.

History

The location of the Isthmus of Corinth; the modern canal is shown in light blue.

Ancient attempts

Several rulers of antiquity dreamed of digging a cutting through the isthmus. The first to propose such an undertaking was the tyrant Periander in the 7th century BC. The project was abandoned and Periander instead constructed a simpler and less costly overland portage road, named the Diolkos or stone carriageway, along which ships could be towed from one side of the isthmus to the other. Periander's change of heart is attributed variously to the great expense of the project, a lack of labour or a fear that a canal would have robbed Corinth of its dominant role as an entrepôt for goods. Remnants of the Diolkos still exist next to the modern canal.

The Diadoch Demetrius Poliorcetes (336–283 BC) planned to construct a canal as a means to improve his communication lines, but dropped the plan after his surveyors, miscalculating the levels of the adjacent seas, feared heavy floods.

The philosopher Apollonius of Tyana prophesied that anyone who proposed to dig a Corinthian canal would be met with illness. Three Roman rulers considered the idea but all suffered violent deaths; the historians Plutarch and Suetonius both wrote that the Roman dictator Julius Caesar considered digging a canal through the isthmus but was assassinated before he could begin the project. Caligula, the third Roman Emperor, commissioned a study in 40 AD from Egyptian experts who claimed incorrectly that the Corinthian Gulf was higher than the Saronic Gulf. As a result, they concluded, if a canal were dug the island of Aegina would be inundated. Caligula's interest in the idea got no further as he too was assassinated before making any progress.

Remains of Nero's canal project in 1881

The emperor Nero was the first to attempt to construct the canal, personally breaking the ground with a pickaxe and removing the first basket-load of soil in 67 AD, but the project was abandoned when he died shortly afterwards. The Roman workforce, consisting of 6,000 Jewish prisoners of war, started digging 40–50-metre-wide (130–160 ft) trenches from both sides, while a third group at the ridge drilled deep shafts for probing the quality of the rock (which were reused in 1881 for the same purpose).

According to Suetonius, the canal was dug to a distance of four stades – approximately 700 metres (2,300 ft) – or about a tenth of the total distance across the isthmus. A memorial of the attempt in the form of a relief of Hercules was left by Nero's workers and can still be seen in the canal cutting today. Other than this, as the modern canal follows the same course as Nero's, no remains have survived.

The Greek philosopher and Roman senator Herodes Atticus is known to have considered digging a canal in the 2nd century AD, but did not get a project under way. The Venetians also considered it in 1687 after their conquest of the Peloponnese but likewise did not initiate a project.

Corinth stone.jpg

Construction of the modern canal

The idea of a canal was revived after Greece gained formal independence from the Ottoman Empire in 1830. The Greek statesman Ioannis Kapodistrias asked a French engineer to assess the feasibility of the project but had to abandon it when its cost was assessed at 40 million gold francs—far too expensive for the newly independent country. Fresh impetus was given by the opening of the Suez Canal in 1869 and the following year, the government of Prime Minister Thrasyvoulos Zaimis passed a law authorizing the construction of a Corinth Canal. French entrepreneurs were put in charge but, following the bankruptcy of the French company that had attempted to dig the Panama Canal, French banks refused to lend money and the company went bankrupt as well. A fresh concession was granted to the Société Internationale du Canal Maritime de Corinthe in 1881, which was commissioned to construct the canal and operate it for the next 99 years. Construction was formally inaugurated on 23 April 1882 in the presence of King George I of Greece.

Share of the company Canal Maritime de Corinthe, issued 1882

The company's initial capital was 30,000,000 francs (US$6.0 million in the money of the day), but after eight years of work it ran out of money and a bid to issue 60,000 bonds of 500 francs each flopped when less than half of the bonds were sold. The company's head, István Türr, went bankrupt, as did the company itself and a bank that had agreed to raise additional funds for the project. Construction resumed in 1890 when the project was transferred to a Greek company, and was completed on 25 July 1893 after eleven years' work.

After completion

The Inauguration of the Corinth Canal (1893) by Konstantinos Volanakis.

The canal experienced financial and operational difficulties after completion. The narrowness of the canal makes navigation difficult. Its high walls channel wind along its length, and the different times of the tides in the two gulfs cause strong tidal currents in the channel. For these reasons, many ship operators were unwilling to use the canal, and traffic was far below predictions. Annual traffic of just under 4 million net tons had been anticipated, but by 1906 traffic had reached only half a million net tons annually. By 1913 the total had risen to 1.5 million net tons, but the disruption caused by World War I resulted in a major decline in traffic.

The Corinth Canal seen from the air, showing the steep limestone walls which proved vulnerable to landslides

Another persistent problem was the heavily faulted nature of the sedimentary rock, in an active seismic zone, through which the canal is cut. The canal's high limestone walls have been persistently unstable from the start. Although it was formally opened in July 1893 it was not opened to navigation until the following November, due to landslides. It was soon found that the wake from ships passing through the canal undermined the walls, causing further landslides. This required further expense in building retaining walls along the water's edge for more than half of the length of the canal, using 165,000 cubic metres of masonry. Between 1893 and 1940, it was closed for a total of four years for maintenance to stabilise the walls. In 1923 alone, 41,000 cubic metres of material fell into the canal, which took two years to clear out.

Serious damage was caused to the canal during World War II. On 26 April 1941, during the Battle of Greece between defending British troops and the invading forces of Nazi Germany, German parachutists and glider troops attempted to capture the main bridge over the canal. The bridge was defended by the British and had been wired for demolition. The Germans surprised the defenders with a glider-borne assault in the early morning of 26 April and captured the bridge, but the British set off the charges and destroyed the structure. Other authors maintain that German pioneers cut the detonation wires, and a lucky hit by British artillery triggered the explosion. The bridge was replaced by a combined rail/road bridge built in 25 days by the IV Railway Engineer Battalion, of the Royal Italian Army's Railway Engineer Regiment.

Three years later, as German forces retreated from Greece, the canal was put out of action by German "scorched earth" operations. German forces used explosives to trigger landslides to block the canal, destroyed the bridges and dumped locomotives, bridge wreckage and other infrastructure into the canal to hinder repairs. The United States Army Corps of Engineers began to clear the canal in November 1947 and reopened it for shallow-draft traffic by 7 July 1948, and for all traffic by that September.

Modern use

Because the canal is difficult to navigate for large vessels, it is mostly used by smaller recreational boats. A notable exception occurred on 9 October 2019, when MS Braemar became the widest and longest ship to cruise through the canal.

Layout

Aerial photograph of the Corinth Canal area (2011)

The canal consists of a single channel 8 metres (26 ft) deep, excavated at sea level (thus requiring no locks), measuring 6,343 metres (20,810 ft) long by 24.6 metres (81 ft) wide at sea level and 21.3 metres (70 ft) wide at the bottom. The rock walls, which rise 90 metres (300 ft) above sea level, are at a near-vertical 80° angle. The canal is crossed by a railway line, a road and a motorway at a height of about 45 metres (148 ft). In 1988 submersible bridges were installed at sea level at each end of the canal, by the eastern harbour of Isthmia and the western harbour of Poseidonia.

Although the canal saves the 700-kilometre (430 mi) journey around the Peloponnese, it is too narrow for modern ocean freighters, as it can accommodate ships only of a width up to 17.6 metres (58 ft) and draft up to 7.3 metres (24 ft). In October 2019, with over 900 passengers on board, a 22.5 metres (74 ft) wide and 195 metres (640 ft) long, Fred. Olsen Cruise Lines cruise ship successfully traversed the canal to set a new record for longest ship to pass through the canal. Ships can pass through the canal only one convoy at a time on a one-way system. Larger ships have to be towed by tugs. The canal is currently used mainly by tourist ships; around 11,000 ships per year travel through the waterway.

Adrenal insufficiency

From Wikipedia, the free encyclopedia

Adrenal insufficiency
Illu adrenal gland.jpg
Adrenal gland
SpecialtyEndocrinology

Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; but may also include impaired production of aldosterone (a mineralocorticoid), which regulates sodium conservation, potassium secretion, and water retention. Craving for salt or salty foods due to the urinary losses of sodium is common.

Addison's disease and congenital adrenal hyperplasia can manifest as adrenal insufficiency. If not treated, adrenal insufficiency may result in abdominal pains, vomiting, muscle weakness and fatigue, depression, low blood pressure, weight loss, kidney failure, changes in mood and personality, and shock (adrenal crisis). An adrenal crisis may occur if the body is subjected to stress, such as an accident, injury, surgery, or severe infection; death may quickly follow.

Adrenal insufficiency can also occur when the hypothalamus or the pituitary gland does not make adequate amounts of the hormones that assist in regulating adrenal function. This is called secondary or tertiary adrenal insufficiency and is caused by lack of production of ACTH in the pituitary or lack of CRH in the hypothalamus, respectively.

Types

There are three major types of adrenal insufficiency.

Signs and symptoms

Signs and symptoms include: hypoglycemia, dehydration, weight loss, and disorientation. Additional signs and symptoms include weakness, tiredness, dizziness, low blood pressure that falls further when standing (orthostatic hypotension), cardiovascular collapse, muscle aches, nausea, vomiting, and diarrhea. These problems may develop gradually and insidiously. Addison's disease can present with tanning of the skin that may be patchy or even all over the body. Characteristic sites of tanning are skin creases (e.g. of the hands) and the inside of the cheek (buccal mucosa). Goitre and vitiligo may also be present. Eosinophilia may also occur.

Causes

Causes of acute adrenal insufficiency are mainly sudden withdrawal of long-term corticosteroid therapy, Waterhouse–Friderichsen syndrome, and stress in people with underlying chronic adrenal insufficiency. The latter is termed critical illness–related corticosteroid insufficiency.

For chronic adrenal insufficiency, the major contributors are autoimmune adrenalitis (Addison's Disease), tuberculosis, AIDS, and metastatic disease. Minor causes of chronic adrenal insufficiency are systemic amyloidosis, fungal infections, hemochromatosis, and sarcoidosis.

Autoimmune adrenalitis may be part of Type 2 autoimmune polyglandular syndrome, which can include type 1 diabetes, hyperthyroidism, and autoimmune thyroid disease (also known as autoimmune thyroiditis, Hashimoto's thyroiditis, and Hashimoto's disease). Hypogonadism may also present with this syndrome. Other diseases that are more common in people with autoimmune adrenalitis include premature ovarian failure, celiac disease, and autoimmune gastritis with pernicious anemia.

Adrenoleukodystrophy can also cause adrenal insufficiency.

Adrenal insufficiency can also result when a patient has a craniopharyngioma, which is a histologically benign tumor that can damage the pituitary gland and so cause the adrenal glands not to function. This would be an example of secondary adrenal insufficiency syndrome.

Causes of adrenal insufficiency can be categorized by the mechanism through which they cause the adrenal glands to produce insufficient cortisol. These are adrenal dysgenesis (the gland has not formed adequately during development), impaired steroidogenesis (the gland is present but is biochemically unable to produce cortisol) or adrenal destruction (disease processes leading to glandular damage).

Corticosteroid withdrawal

Use of high-dose steroids for more than a week begins to produce suppression of the person's adrenal glands because the exogenous glucocorticoids suppress release of hypothalamic corticotropin-releasing hormone (CRH) and pituitary adrenocorticotropic hormone (ACTH). With prolonged suppression, the adrenal glands atrophy (physically shrink), and can take months to recover full function after discontinuation of the exogenous glucocorticoid. During this recovery time, the person is vulnerable to adrenal insufficiency during times of stress, such as illness, due to both adrenal atrophy and suppression of CRH and ACTH release. Use of steroids joint injections may also result in adrenal suppression after discontinuation.

Adrenal dysgenesis

All causes in this category are genetic, and generally very rare. These include mutations to the SF1 transcription factor, congenital adrenal hypoplasia due to DAX-1 gene mutations and mutations to the ACTH receptor gene (or related genes, such as in the Triple A or Allgrove syndrome). DAX-1 mutations may cluster in a syndrome with glycerol kinase deficiency with a number of other symptoms when DAX-1 is deleted together with a number of other genes.

Impaired steroidogenesis

To form cortisol, the adrenal gland requires cholesterol, which is then converted biochemically into steroid hormones. Interruptions in the delivery of cholesterol include Smith–Lemli–Opitz syndrome and abetalipoproteinemia.

Of the synthesis problems, congenital adrenal hyperplasia is the most common (in various forms: 21-hydroxylase, 17α-hydroxylase, 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase), lipoid CAH due to deficiency of StAR and mitochondrial DNA mutations. Some medications interfere with steroid synthesis enzymes (e.g. ketoconazole), while others accelerate the normal breakdown of hormones by the liver (e.g. rifampicin, phenytoin).

Adrenal destruction

Autoimmune adrenalitis is the most common cause of Addison's disease in the industrialised world. Autoimmune destruction of the adrenal cortex is caused by an immune reaction against the enzyme 21-hydroxylase (a phenomenon first described in 1992). This may be isolated or in the context of autoimmune polyendocrine syndrome (APS type 1 or 2), in which other hormone-producing organs, such as the thyroid and pancreas, may also be affected.

Adrenal destruction is also a feature of adrenoleukodystrophy (ALD), and when the adrenal glands are involved in metastasis (seeding of cancer cells from elsewhere in the body, especially lung), hemorrhage (e.g. in Waterhouse–Friderichsen syndrome or antiphospholipid syndrome), particular infections (tuberculosis, histoplasmosis, coccidioidomycosis), or the deposition of abnormal protein in amyloidosis.

Pathophysiology

Hyponatremia can be caused by glucocorticoid deficiency. Low levels of glucocorticoids leads to systemic hypotension (one of the effects of cortisol is to increase peripheral resistance), which results in a decrease in stretch of the arterial baroreceptors of the carotid sinus and the aortic arch. This removes the tonic vagal and glossopharyngeal inhibition on the central release of ADH: high levels of ADH will ensue, which will subsequently lead to increase in water retention and hyponatremia.

Differently from mineralocorticoid deficiency, glucocorticoid deficiency does not cause a negative sodium balance (in fact a positive sodium balance may occur).

Diagnosis

The best diagnostic tool to confirm adrenal insufficiency is the ACTH stimulation test; however, if a patient is suspected to be suffering from an acute adrenal crisis, immediate treatment with IV corticosteroids is imperative and should not be delayed for any testing, as the patient's health can deteriorate rapidly and result in death without replacing the corticosteroids.

Dexamethasone should be used as the corticosteroid if the plan is to do the ACTH stimulation test at a later time as it is the only corticosteroid that will not affect the test results.

If not performed during crisis, then labs to be run should include: random cortisol, serum ACTH, aldosterone, renin, potassium and sodium. A CT of the adrenal glands can be used to check for structural abnormalities of the adrenal glands. An MRI of the pituitary can be used to check for structural abnormalities of the pituitary. However, in order to check the functionality of the Hypothalamic Pituitary Adrenal (HPA) Axis the entire axis must be tested by way of ACTH stimulation test, CRH stimulation test and perhaps an Insulin Tolerance Test (ITT). In order to check for Addison's Disease, the auto-immune type of primary adrenal insufficiency, labs should be drawn to check 21-hydroxylase autoantibodies.

 

Cushing's syndrome

From Wikipedia, the free encyclopedia

Cushing's syndrome
Other namesHypercortisolism, Itsenko-Cushing syndrome, hyperadrenocorticism
CushingsFace.jpg
Person's facial appearance 3 months after treatment with inhaled fluticasone
SpecialtyEndocrinology
SymptomsHigh blood pressure, abdominal obesity with thin arms and legs, reddish stretch marks, round red face, fat lump between the shoulders, weak muscles, acne, fragile skin
Usual onset20–50 years
CausesProlonged exposure to cortisol
Diagnostic methodRequires a number of steps
mentBased on underlying cause
PrognosisGenerally good with treatment
Frequency2–3 per million people per year

Cushing's syndrome is the collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly. Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.

Cushing's syndrome is caused by either excessive cortisol-like medication, such as prednisone, or a tumor that either produces or results in the production of excessive cortisol by the adrenal glands. Cases due to a pituitary adenoma are known as Cushing's disease, which is the second most common cause of Cushing's syndrome after medication. A number of other tumors may also cause Cushing's.  Some of these are associated with inherited disorders such as multiple endocrine neoplasia type 1 and Carney complex. Diagnosis requires a number of steps. The first step is to check the medications a person takes. The second step is to measure levels of cortisol in the urine, saliva or in the blood after taking dexamethasone. If this test is abnormal, the cortisol may be measured late at night. If the cortisol remains high, a blood test for ACTH may be done.

Most cases can be treated and cured. If due to medications, these can often be slowly decreased if still required or slowly stopped. If caused by a tumor, it may be treated by a combination of surgery, chemotherapy, and/or radiation. If the pituitary was affected, other medications may be required to replace its lost function. With treatment, life expectancy is usually normal. Some, in whom surgery is unable to remove the entire tumor, have an increased risk of death.

About two to three people per million are affected each year. It most commonly affects people who are 20 to 50 years of age. Women are affected three times more often than men. A mild degree of overproduction of cortisol without obvious symptoms, however, is more common. Cushing's syndrome was first described by American neurosurgeon Harvey Cushing in 1932. Cushing's syndrome may also occur in other animals including cats, dogs, and horses.

Signs and symptoms

Symptoms of Cushing's syndrome
 
Increased hair and stria in a person with medication-induced Cushing's syndrome
 
Features of Cushing syndrome including a round face, acne, reddish skin, central obesity, and poor muscle tone

Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity). Common signs include the growth of fat pads along the collarbone, on the back of the neck ("buffalo hump" or lipodystrophy), and on the face ("moon face"). Other symptoms include excess sweating, dilation of capillaries, thinning of the skin (which causes easy bruising and dryness, particularly the hands) and mucous membranes, purple or red striae (the weight gain in Cushing's syndrome stretches the skin, which is thin and weakened, causing it to hemorrhage) on the trunk, buttocks, arms, legs, or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth), baldness and/or extremely dry and brittle hair. In rare cases, Cushing's can cause hypocalcemia. The excess cortisol may also affect other endocrine systems and cause, for example, insomnia, inhibited aromatase, reduced libido, impotence in men, and amenorrhoea, oligomenorrhea and infertility in women due to elevations in androgens. Studies have also shown that the resultant amenorrhea is due to hypercortisolism, which feeds back onto the hypothalamus resulting in decreased levels of GnRH release.

Many of the features of Cushing's are those seen in metabolic syndrome, including insulin resistance, hypertension, obesity, and elevated blood levels of triglycerides.

Cognitive conditions, including memory and attention dysfunctions, as well as depression, are commonly associated with elevated cortisol, and may be early indicators of exogenous or endogenous Cushing's. Depression and anxiety disorders are also common.

Other striking and distressing skin changes that may appear in Cushing's syndrome include facial acne, susceptibility to superficial fungus (dermatophyte and malassezia) infections, and the characteristic purplish, atrophic striae on the abdomen.

Other signs include increased urination (and accompanying increased thirst), persistent high blood pressure (due to cortisol's enhancement of epinephrine's vasoconstrictive effect) and insulin resistance (especially common with ACTH production outside the pituitary), leading to high blood sugar and insulin resistance which can lead to diabetes mellitus. Insulin resistance is accompanied by skin changes such as acanthosis nigricans in the axilla and around the neck, as well as skin tags in the axilla. Untreated Cushing's syndrome can lead to heart disease and increased mortality. Cortisol can also exhibit mineralocorticoid activity in high concentrations, worsening the hypertension and leading to hypokalemia (common in ectopic ACTH secretion) and hypernatremia (increased Na+ ions concentration in plasma). Furthermore, excessive cortisol may lead to gastrointestinal disturbances, opportunistic infections, and impaired wound healing related to cortisol's suppression of the immune and inflammatory responses. Osteoporosis is also an issue in Cushing's syndrome since osteoblast activity is inhibited. Additionally, Cushing's syndrome may cause sore and aching joints, particularly in the hip, shoulders, and lower back.

Brain changes such as cerebral atrophy may occur. This atrophy is associated with areas of high glucocorticoid receptor concentrations such as the hippocampus and correlates highly with psychopathological personality changes.

Hyperpigmentation

Cushing's syndrome due to excess ACTH may also result in hyperpigmentation. This is due to melanocyte-Stimulating Hormone production as a byproduct of ACTH synthesis from pro-opiomelanocortin (POMC). Alternatively, it is proposed that the high levels of ACTH, β-lipotropin, and γ-lipotropin, which contain weak MSH function, can act on the melanocortin 1 receptor. A variant of Cushing's disease can be caused by ectopic, i.e. extrapituitary, ACTH production from, for example, a small-cell lung cancer.

When Cushing's syndrome is caused by an increase of cortisol at the level of the adrenal glands (via an adenoma or hyperplasia), negative feedback ultimately reduces ACTH production in the pituitary. In these cases, ACTH levels remain low and no hyperpigmentation develops.

Causes

Cushing's syndrome may result from any cause of increased glucocorticoid levels, whether due to medication or internal processes. Some sources however do not consider the glucocorticoid medication-induced condition as "Cushing's syndrome" proper, instead using the term "Cushingoid" to describe the medication's side effects which mimic the endogenous condition.

Cushing's disease is a specific type of Cushing's syndrome caused by a pituitary tumor leading to excessive production of ACTH (adrenocorticotropic hormone). Excessive ACTH stimulates the adrenal cortex to produce high levels of cortisol, producing the disease state. While all Cushing's disease gives Cushing's syndrome, not all Cushing's syndrome is due to Cushing's disease. Several possible causes of Cushing's syndrome are known.

Exogenous

The most common cause of Cushing's syndrome is the use of prescribed glucocorticoids to treat other diseases (iatrogenic Cushing's syndrome). Glucocorticoids are used in treatment of a variety of disorders, including asthma and rheumatoid arthritis, and also used for immunosuppression after organ transplants. Administration of synthetic ACTH is also possible, but ACTH is less often prescribed due to cost and lesser utility. Rarely, Cushing's syndrome can also be due to the use of medroxyprogesterone acetate. In exogenous Cushing's, the adrenal glands may often gradually atrophy due to lack of stimulation by ACTH, the production of which is suppressed by glucocorticoid medication. Abruptly stopping the medication can thus result in acute and potentially life-threatening adrenal insufficiency and the dose must hence be slowly and carefully tapered off to allow internal cortisol production to pick up. In some cases, patients never recover sufficient levels of internal production and must continue taking glucocorticoids at physiological doses for life.

Cushing's syndrome in childhood is especially rare and usually results from use of glucocorticoid medication.

Endogenous

Endogenous Cushing's syndrome results from some derangement of the body's own system of cortisol secretion. Normally, ACTH is released from the pituitary gland when necessary to stimulate the release of cortisol from the adrenal glands.

  • In pituitary Cushing's, a benign pituitary adenoma secretes ACTH. This is also known as Cushing's disease and is responsible for 70% of endogenous Cushing's syndrome.
  • In adrenal Cushing's, excess cortisol is produced by adrenal gland tumors, hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia.
  • Tumors outside the normal pituitary-adrenal system can produce ACTH (occasionally with CRH) that affects the adrenal glands. This etiology is called ectopic or paraneoplastic Cushing's disease and is seen in diseases such as small cell lung cancer.
  • Finally, rare cases of CRH-secreting tumors (without ACTH secretion) have been reported, which stimulates pituitary ACTH production.

Pseudo-Cushing's syndrome

Elevated levels of total cortisol can also be due to estrogen found in oral contraceptive pills that contain a mixture of estrogen and progesterone, leading to pseudo-Cushing's syndrome. Estrogen can cause an increase of cortisol-binding globulin and thereby cause the total cortisol level to be elevated. However, the total free cortisol, which is the active hormone in the body, as measured by a 24-hour urine collection for urinary free cortisol, is normal.

Pathophysiology

The hypothalamus is in the brain and the pituitary gland sits just below it. The paraventricular nucleus (PVN) of the hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release adrenocorticotropin (ACTH). ACTH travels via the blood to the adrenal gland, where it stimulates the release of cortisol. Cortisol is secreted by the cortex of the adrenal gland from a region called the zona fasciculata in response to ACTH. Elevated levels of cortisol exert negative feedback on CRH in the hypothalamus, which decreases the amount of ACTH released from the anterior pituitary gland.

Strictly, Cushing's syndrome refers to excess cortisol of any etiology (as syndrome means a group of symptoms). One of the causes of Cushing's syndrome is a cortisol-secreting adenoma in the cortex of the adrenal gland (primary hypercortisolism/hypercorticism). The adenoma causes cortisol levels in the blood to be very high, and negative feedback on the pituitary from the high cortisol levels causes ACTH levels to be very low.

Cushing's disease refers only to hypercortisolism secondary to excess production of ACTH from a corticotroph pituitary adenoma (secondary hypercortisolism/hypercorticism) or due to excess production of hypothalamus CRH (Corticotropin releasing hormone) (tertiary hypercortisolism/hypercorticism). This causes the blood ACTH levels to be elevated along with cortisol from the adrenal gland. The ACTH levels remain high because the tumor is unresponsive to negative feedback from high cortisol levels.

When Cushing's syndrome is due to extra ACTH it is known as ectopic Cushing syndrome. This may be seen in a paraneoplastic syndrome.

When Cushing's syndrome is suspected, either a dexamethasone suppression test (administration of dexamethasone and frequent determination of cortisol and ACTH level), or a 24-hour urinary measurement for cortisol offers equal detection rates. Dexamethasone is a glucocorticoid and simulates the effects of cortisol, including negative feedback on the pituitary gland. When dexamethasone is administered and a blood sample is tested, cortisol levels >50 nmol/l (1.81 μg/dl) would be indicative of Cushing's syndrome because an ectopic source of cortisol or ACTH (such as adrenal adenoma) exists which is not inhibited by the dexamethasone. A novel approach, recently cleared by the US FDA, is sampling cortisol in saliva over 24 hours, which may be equally sensitive, as late-night levels of salivary cortisol are high in cushingoid patients. Other pituitary hormone levels may need to be ascertained. Performing a physical examination to determine any visual field defect may be necessary if a pituitary lesion is suspected, which may compress the optic chiasm, causing typical bitemporal hemianopia.

When any of these tests is positive, CT scanning of the adrenal gland and MRI of the pituitary gland are performed to detect the presence of any adrenal or pituitary adenomas or incidentalomas (the incidental discovery of harmless lesions). Scintigraphy of the adrenal gland with iodocholesterol scan is occasionally necessary. Occasionally, determining the ACTH levels in various veins in the body by venous catheterization, working towards the pituitary (petrosal sinus sampling) is necessary. In many cases, the tumors causing Cushing's disease are less than 2 mm in size and difficult to detect using MRI or CT imaging. In one study of 261 patients with confirmed pituitary Cushing's disease, only 48% of pituitary lesions were identified using MRI prior to surgery.

Plasma CRH levels are inadequate at diagnosis (with the possible exception of tumors secreting CRH) because of peripheral dilution and binding to CRHBP.

Diagnosis

Cushing's syndrome can be ascertained via a variety of test which include the following:

Treatment

Most cases of Cushingoid symptoms are caused by corticosteroid medications, such as those used for asthma, arthritis, eczema and other inflammatory conditions. Consequently, most patients are effectively treated by carefully tapering off (and eventually stopping) the medication that causes the symptoms.

If an adrenal adenoma is identified, it may be removed by surgery. An ACTH-secreting corticotrophic pituitary adenoma should be removed after diagnosis. Regardless of the adenoma's location, most patients require steroid replacement postoperatively at least in the interim, as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed, replacement with hydrocortisone or prednisolone is imperative.

In those patients not suited for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone) but they are of limited efficacy. Mifepristone is a powerful glucocorticoid type II receptor antagonist and, since it does not interfere with normal cortisol homeostasis type I receptor transmission, may be especially useful for treating the cognitive effects of Cushing's syndrome. However, the medication faces considerable controversy due to its use as an abortifacient. In February 2012, the FDA approved mifepristone to control high blood sugar levels (hyperglycemia) in adult patients who are not candidates for surgery, or who did not respond to prior surgery, with the warning that mifepristone should never be used by pregnant women. In March 2020, Isturisa (osilodrostat) oral tablets a 11-beta-hydroxylase enzyme inhibitor was approved by FDA for treating those patients who cannot undergo pituitary surgery or for patients who underwent surgery but continues to have the disease.

Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol. In some occasions, this removes negative feedback from a previously occult pituitary adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to hyperpigmentation. This clinical situation is known as Nelson's syndrome.

Epidemiology

Cushing's syndrome caused by treatment with corticosteroids is the most common form. Cushing's disease is rare; a Danish study found an incidence of less than one case per million people per year. However, asymptomatic microadenomas (less than 10 mm in size) of the pituitary are found in about one in six individuals.

People with Cushing's syndrome have increased morbidity and mortality as compared to the general population. The most common cause of mortality in Cushing's syndrome is cardiovascular events. People with Cushing's syndrome have nearly 4 times increased cardiovascular mortality as compared to the general population.

Neurophilosophy

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