Due to the strong link between PPID and insulin resistance, testing is recommended for all horses suspected or confirmed to be suffering from PPID. There are two tests commonly used for insulin resistance: the oral sugar test and fasting insulin blood concentration.

The fasting insulin concentration involves giving a horse a single flake of hay at 10 pm the night before testing, with blood being drawn the following morning. Both insulin and glucose blood levels are measured. Hyperinsulinemia suggests insulin resistance, but normal or low fasting insulin does not rule out PPID. This test is easy to perform, but is less sensitive than the oral sugar test. It is best used in cases where risks of laminitis make the oral sugar test potentially unsafe.

The oral sugar test also requires giving the horse only a single flake of hay at 10pm the night before the test. The following morning, karo corn syrup is given orally, and glucose and insulin levels are measured at 60 and 90 minutes after administration. Normal or excessively high insulin levels are diagnostic. However, equivocal test results require retesting at a later date, or performing a different test. A similar test is available outside the US, in areas where corn-syrup products are less readily available, where horses are given a morning meal of chaff with dextrose powder, and blood insulin levels are measured 2 hours later.

The dexamethasone suppression test involves administering dexamethasone, a synthetic glucocorticoid, to the horse, and measuring its serum cortisol levels before and 19–24 hours after injection. In a normal horse, dexamethasone administration results in negative feedback to the pituitary, resulting in decreased ACTH production from the pars distalis and, therefore, decreased synthesis of cortisol at the level of the adrenal gland. A horse with PPID, which has an overactive pars intermedia not regulated by glucocorticoid levels, does not suppress ACTH production and, therefore, cortisol levels remain high. False negatives can occur in early disease. Additionally, dexamethasone administration may increase the risk of laminitis in horses already prone to the disease. For these reasons, the dexamethasone suppression test is currently not recommended for PPID testing.

Diagnosis is made first by diagnosing Cushing's syndrome, which can be difficult to do clinically since the most characteristic symptoms only occur in a minority of patients. Some of the biochemical diagnostic tests used include salivary and blood serum cortisol testing, 24-hour urinary free cortisol (UFC) testing, the dexamethasone suppression test (DST), and bilateral inferior petrosal sinus sampling (BIPSS). No single test is perfect and multiple tests should always be used to achieve a proper diagnosis. Diagnosing Cushing's disease is a multidisciplinary process involving doctors, endocrinologists, radiologists, surgeons, and chemical pathologists.

Once Cushing's syndrome has been diagnosed, the first step towards finding the cause is measuring plasma corticotropin concentrations. A concentration consistently below 1.1 pmol/L is classified as corticotropin-independent and does not lead to a diagnosis of Cushing's disease. In such cases, the next step is adrenal imaging with CT. If plasma corticotropin concentrations are consistently above 3.3 pmol/L, then corticotropin-dependent Cushing's syndrome is most likely. Any intermediate values need to be cautiously interpreted and a corticotropin-releasing hormone (CRH) test is advised in order to confirm corticotropin dependency. If corticotropin-dependent Cushing's syndrome is determined then the next step is to distinguish between Cushing's disease and ectopic corticotropin syndrome. This is done via a combination of techniques including CRH, high-dose DST, BIPSS, and pituitary MRI.

Two dexamethasone suppression tests (DSTs) are generally used, the overnight and 48-h DSTs. For both tests, a plasma cortisol level above 50 nmol/L is indicative of Cushing's disease. However, 3-8% of patients with Cushing's disease will test negative due to a retention of dexamethasone suppression abilities. For non-Cushing or healthy patients, the false-positive rate is 30%. The 48-h DST is advantageous since it is more specific and can be done by outpatients upon proper instruction. In the high-dose 48-h DST, 2 mg of dexamethasone is given every 6 hours for 48 hours or a single dose of 8 mg is given. This test is not needed if the 48-h low-dose DST has shown suppression of cortisol by over 30%. These tests are based on the glucocorticoid sensitivity of pituitary adenomas compared to non-pituitary tumors.

Administration of corticotropin releasing hormone (CRH) can differentiate this condition from ectopic ACTH secretion. In a patient with Cushing's disease, the tumor cells will be stimulated to release corticotropin and elevated plasma corticotropin levels will be detected. This rarely occurs with ectopic corticotropin syndrome and thus is quite useful for distinguishing between the two conditions. If ectopic, the plasma ACTH and cortisol levels should remain unchanged; if this is pituitary related, levels of both would rise. The CRH test uses recombinant human or bovine-sequence CRH, which is administered via a 100μg intravenous bolus dose. The sensitivity of the CRH test for detecting Cushing's disease is 93% when plasma levels are measured after fifteen and thirty minutes. However, this test is used only as a last resort due to its high cost and complexity.

A CT or MRI of the pituitary may also show the ACTH secreting tumor if present. However, in 40% of Cushing's disease patients MRI is unable to detect a tumor. In one study of 261 patients with confirmed pituitary Cushing's disease, only 48% of pituitary lesions were identified using MRI prior to surgery. The average size of tumor, both those that were identified on MRI and those that were only discovered during surgery, was 6 mm.

A more accurate but invasive test used to differentiate pituitary from ectopic or adrenal Cushing's syndrome is inferior petrosal sinus sampling. A corticotropin gradient sample via BIPSS is required to confirm diagnosis when pituitary MRI imaging and biochemical diagnostic tests have been inconclusive. A basal central:peripheral ratio of over 3:1 when CRH is administered is indicative of Cushing’s disease. This test has been the gold standard for distinguishing between Cushing's disease and ectopic corticotropin syndrome. The BIPSS has a sensitivity and specificity of 94% for Cushing's disease but it is usually used as a last resort due to its invasiveness, rare but serious complications, and the expertise required to perform it.

Another diagnostic test used is the urinary free cortisol (UFC) test, which measures the excess cortisol excreted by the kidneys into the urine. Results of 4x higher cortisol levels than normal are likely to be Cushing's disease. This test should be repeated three times in order to exclude any normally occurring periods of hypercortisolism. The UFC test has a specificity of 81% and thus has a high rate of false-positives that are due to pseudo-Cushing states, sleep apnea, polycystic ovary syndrome, familial glucocorticoid resistance, and hyperthyroidism.

The late-night or midnight salivary cortisol test has been gaining support due to its ease of collection and stability at room temperature, therefore it can be assigned to outpatients. The test measures free circulating cortisol and has both a sensitivity and specificity of 95-98%. This test is especially useful for diagnosing children.

Few women of childbearing age have high blood pressure, up to 11% develop hypertension of pregnancy. While generally benign, it may herald three complications of pregnancy: pre-eclampsia, HELLP syndrome and eclampsia. Follow-up and control with medication is therefore often necessary.

There are differenct types of congenital hyperinsulinism as "diffuse and focal" indicated below:

For the diagnosis of hyperpituitarism it depends on the cell type(s) affected, clinical manifestations of hormone excess may include, gigantism or acromegaly, which can be identified by clinical and radiographic results. Cushing's disease diagnosis is done with a physical examination, laboratory tests and X rays of the pituitary glands (to locate tumors) For prolactinoma, diagnosis comes in the form of the measurement of serum prolactin levels and x-ray of pituitary gland.

Certain medications, including NSAIDs (Motrin/Ibuprofen) and steroids can cause hypertension. Other medications include extrogens (such as those found in oral contraceptives with high estrogenic activity), certain antidepressants (such as venlafaxine), buspirone, carbamazepine, bromocriptine, clozapine, and cyclosporine.

High blood pressure that is associated with the sudden withdrawal of various antihypertensive medications is called rebound hypertension. The increases in blood pressure may result in blood pressures greater than when the medication was initiated. Depending on the severity of the increase in blood pressure, rebound hypertension may result in a hypertensive emergency. Rebound hypertension is avoided by gradually reducing the dose (also known as "dose tapering"), thereby giving the body enough time to adjust to reduction in dose. Medications commonly associated with rebound hypertension include centrally-acting antihypertensive agents, such as clonidine and methyl-dopa.

Other herbal or "natural products" which have been associated with hypertension include ma huang, St John's wort, and licorice.

In terms of the investigation of congenital hyperinsulinism, valuable diagnostic information is obtained from a blood sample drawn during hypoglycemia, detectable amounts of insulin during hypoglycemia are abnormal and indicate that hyperinsulinism is likely to be the cause. Inappropriately low levels of free fatty acids and ketones provide additional evidence of insulin excess. An additional piece of evidence indicating hyperinsulinism is a usually high requirement for intravenous glucose to maintain adequate glucose levels, the minimum glucose required to maintain a plasma glucose above 70 mg/dl. A GIR above 8 mg/kg/minute in infancy suggests hyperinsulinism. A third form of evidence suggesting hyperinsulinism is a rise of the glucose level after injection of glucagon at the time of the low glucose.

Diagnostic efforts then shift to determining the type- elevated ammonia levels or abnormal organic acids can indicate specific, rare types. Intrauterine growth retardation and other perinatal problems raise the possibility of transience, while large birthweight suggests one of the more persistent conditions. Genetic screening is now available within a useful time frame for some of the specific conditions.It is worthwhile to identify the minority of severe cases with focal forms of hyperinsulinism because these can be completely cured by partial pancreatectomy. A variety of pre-operative diagnostic procedures have been investigated but none has been established as infallibly reliable. Positron emission tomography is becoming the most useful imaging technique.

Most Cushing's syndrome cases 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 homeostatis 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.

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.

Treatment (for hyperpituitarism) in the case of prolactinoma consists of long-term medical management. Dopamine agonists are strong suppressors of PRL secretion and establish normal gonadal function. It also inhibits tumor cell replication (in some cases causes tumor shrinkage) Treatment for gigantism begins with establishing target goals for IGF-1, transsphenoidal surgery (somatostatin receptor ligands- preoperatively) and postoperative imaging assessment. For Cushing's disease there is surgery to extract the tumor; after surgery, the gland may slowly start to work again, though not always.

Diagnosis usually occurs upon investigation of a cause for already suspected Cushing's syndrome. High levels of cortisol observed in patients with PPNAD are not suppressed upon administration of dexamethasone (dexamethasone suppression test), and upon MRI or CT imaging, the pituitary will show no abnormalities. Measuring ACTH will confirm that the cause of the patients Cushing's syndrome is ACTH independent. The nature of Cushing's syndrome itself is periodic, which can make diagnosing PPNAD increasingly difficult.

Diagnosis of PPNAD can be difficult to determine preoperatively as CT scan findings can be variable ie appear normal or suggest unilateral adrenal lesions therefore impeding the correct diagnosis. NP-59 scintigraphy may be particularly useful in identifying the bilateral nature of the disease.

Gene studies are not necessary for diagnosis as there are clear gross and histological diagnostic markers, as the nodules can usually be seen clearly in both cases A positive family history of PPNAD has been shown to be associated with abnormal histological findings, e.g. mitotic figures, which may further hinder diagnosis. At the point where abdominal CT scanning and pituitary fossa MRI show no clear abnormalities, adrenalectomy may be performed.

An adrenal "incidentaloma" is an adrenal tumor found by coincidence without clinical symptoms or suspicion. It is one of the more common unexpected findings revealed by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasonography.

In these cases, a dexamethasone suppression test is often used to detect cortisol excess, and metanephrines or catecholamines for excess of these hormones. Tumors under 3 cm are generally considered benign and are only treated if there are grounds for a diagnosis of Cushing's syndrome or pheochromocytoma. Radiodensity gives a clue in estimating malignancy risk, wherein a tumor with 10 Hounsfield units or less on an unenhanced CT is probably a lipid-rich adenoma.

Hormonal evaluation includes:

- 1-mg overnight dexamethasone suppression test

- 24-hour urinary specimen for measurement of fractionated metanephrines and catecholamines

- Blood plasma aldosterone concentration and plasma renin activity, "if hypertension is present"

On CT scan, benign adenomas typically are of low radiographic density (due to fat content) and show rapid washout of contrast medium (50% or more of the contrast medium washes out at 10 minutes). If the hormonal evaluation is negative and imaging suggests benign, followup should be considered with imaging at 6, 12, and 24 months and repeat hormonal evaluation yearly for 4 years

The first-line treatment of Cushing's disease is surgical resection of ACTH-secreting pituitary adenoma; this surgery involves removal of the tumor via transsphenoidal surgery (TSS).

There are two possible options for access to sphenoidal sinus including of endonosal approach (through the nostril) or sublabial approach (through an incision under the upper lip); many factors such as the size of nostril, the size of the lesion, and the preferences of the surgeon cause the selection of one access route over the other.

Some tumors do not contain a discrete border between tumor and pituitary gland; therefore, careful sectioning through pituitary gland may be required to identify the location of tumor. The probability of successful resection is higher in patients where the tumor was identified at initial surgery in comparison to patients where no tumor was found initially; the overall remission rates in patients with microadenomas undergoing TSS are in range of 65%-90%, and the remission rate in patients with macroadenomas are lower than 65%. patients with persistent disease after initial surgery are treated with repeated pituitary surgery as soon as the active persistent disease is evident; however, reoperation has lower success rate and increases the risk of pituitary insufficiency.

Pituitary radiation therapy is another option for treatment of postoperative persisting hypercortisolemia following unsuccessful transsphenoidal surgery. External-beam pituitary RT is more effective treatment for pediatric CD in children with cure rates of 80%-88%. Hypopituitarism specifically growth hormone deficiency has been reported as the only most common late morbidity of this treatment; GHD has been reported in 36% and 68% of the patients undergoing post pituitary RT for Cushing's disease.

Bilateral adrenalectomy is another treatment which provides immediate reduction of cortisol level and control of hypercortisolism. However, it requires education of patients, because lifelong glucocorticoid and mineralocorticoid replacement therapy is needed for these patients. One of the major complications of this treatment is progression of Nelson's syndrome which is caused by enhance level of tumor growth and ACTH secretion post adrenalectomy in 8%-29% of patients with CD.

During post surgical recovery, patients collect 24-hour urine sample and blood sample for detecting the level of cortisol with the purpose of cure test; level of cortisol near the detection limit assay, corresponds to cure. Hormonal replacement such as steroid is given to patients because of steroid withdrawal. After the completion of collecting urine and blood samples, patients are asked to switch to glucocorticoid such as prednisone to decrease symptoms associated with adrenal withdrawal.

A study of 3,525 cases of TSS for Cushing's disease in the nationally representative

sample of US hospitals between 1993 and 2002 was conducted and revealed the following results: the in-hospital mortality rate was 0.7%; the complication rate was 42.1%. Diabetes insipidus (15%), fluid and electrolyte abnormalities (12.5%), and neurological deficits (5.6%) were the most common complications reported. The analyses of the study show that complications were more likely in patients with pre-operative comorbidities. Patients older than 64 years were more likely to have an adverse outcome and prolonged hospital stay. Women were 0.3 times less likely to have adverse outcomes in comparison to men.

The gold standard for investigating and quantifying insulin resistance is the "hyperinsulinemic euglycemic clamp," so-called because it measures the amount of glucose necessary to compensate for an increased insulin level without causing hypoglycemia. It is a type of glucose clamp technique. The test rarely is performed in clinical care, but is used in medical research, for example, to assess the effects of different medications. The rate of glucose infusion commonly is referred to in diabetes literature as the GINF value.

The procedure takes about two hours. Through a peripheral vein, insulin is infused at 10–120 mU per m per minute. In order to compensate for the insulin infusion, glucose 20% is infused to maintain blood sugar levels between 5 and 5.5 mmol/L. The rate of glucose infusion is determined by checking the blood sugar levels every five to ten minutes.

The rate of glucose infusion during the last thirty minutes of the test determines insulin sensitivity. If high levels (7.5 mg/min or higher) are required, the patient is insulin-sensitive. Very low levels (4.0 mg/min or lower) indicate that the body is resistant to insulin action. Levels between 4.0 and 7.5 mg/min are not definitive, and suggest "impaired glucose tolerance," an early sign of insulin resistance.

This basic technique may be enhanced significantly by the use of glucose tracers. Glucose may be labeled with either stable or radioactive atoms. Commonly used tracers are 3-H glucose (radioactive), 6,6 H-glucose (stable) and 1-C Glucose (stable). Prior to beginning the hyperinsulinemic period, a 3h tracer infusion enables one to determine the basal rate of glucose production. During the clamp, the plasma tracer concentrations enable the calculation of whole-body insulin-stimulated glucose metabolism, as well as the production of glucose by the body (i.e., endogenous glucose production).

Another measure of insulin resistance is the modified insulin suppression test developed by Gerald Reaven at Stanford University. The test correlates well with the euglycemic clamp, with less operator-dependent error. This test has been used to advance the large body of research relating to the metabolic syndrome.

Patients initially receive 25 μg of octreotide (Sandostatin) in 5 mL of normal saline over 3 to 5 minutes via intravenous infusion (IV) as an initial bolus, and then, are infused continuously with an intravenous infusion of somatostatin (0.27 μg/m/min) to suppress endogenous insulin and glucose secretion. Next, insulin and 20% glucose are infused at rates of 32 and 267 mg/m/min, respectively. Blood glucose is checked at zero, 30, 60, 90, and 120 minutes, and thereafter, every 10 minutes for the last half-hour of the test. These last four values are averaged to determine the steady-state plasma glucose level (SSPG). Subjects with an SSPG greater than 150 mg/dL are considered to be insulin-resistant.

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.

Common diagnostic techniques include:

- MRIs

- CAT scans

- blood samples.

Blood samples are assessed for the absence or presence of aldosterone and cortisol. Physical examinations are also useful in patients in order to examine vision, skin pigmentation, how the body replaces steroids, and the cranial nerves. Recent advancements in high-resolution MRIs allow for adenomas to be detected during the early stages of Nelson syndrome. Physical examination including height, weight, vital signs, blood pressure, eye examination, thyroid examination, abdominal examination, neurological examination, skin examination and pubertal staging needs to be assessed. Through blood pressure and pulse readings can indicate hypothyroidism and adrenal insufficiency. Hyper-pigmentation, hyporeflexia, and loss of vision can also indicate Nelson's syndrome when assessed together. Specifically for a child who might have Nelson's syndrome, the patient should be questioned about the symptoms of the disease, and well as symptoms of other diseases to narrow down which disease the patient presents with. The patient should be questioned about how often and to what degree headaches, visual disturbances, and symptoms associated with pituitary malfunction occur. Additionally, adrenal steroid replacement should be assessed, especially in children who have prior insufficiency associated wit

After diagnosis, it is important for patients to be continually monitored. The most common treatment for PPNAD is bilateral laparoscopic adrenalectomy; the process by which both adrenal glands are removed by a small incision.

Patients who have received this treatment will be prescribed mineralocorticoid and glucocorticoid steroids as they are no longer being naturally produced.

This is a treatment which has been used and refined since 1984.

Common treatments for Nelson's syndrome include radiation or surgical procedure. Radiation allows for the limitation of the growth of the pituitary gland and the adenomas. If the adenomas start to affect the surrounding structures of the brain, then a micro-surgical technique can be adapted in order to remove the adenomas in a transsphenoidal (bone at base of the skull) process. Death may result with development of a locally aggressive pituitary tumor. However, does not commonly occur with pituitary diseases. In the rare case, ACTH-secreting tumors can become malignant. Morbidity from the disease can occur due to pituitary tissue compression or replacement, and compression of structures that surround the pituitary fossa. The tumor can also compress the optic apparatus, disturb cerebrospinal fluid flow, meningitis, and testicular enlargement in rare cases.

The U.S. Preventive Services Task Force in 2008 strongly recommends routine screening for men 35 years and older and women 45 years and older for lipid disorders and the treatment of abnormal lipids in people who are at increased risk of coronary heart disease. They also recommend routinely screening men aged 20 to 35 years and women aged 20 to 45 years if they have other risk factors for coronary heart disease. In 2016 they concluded that testing the general population under the age of 40 without symptoms is of unclear benefit.

In Canada, screening is recommended for men 40 and older and women 50 and older. In those with normal cholesterol levels, screening is recommended once every five years. Once people are on a statin further testing provides little benefit except to possibly determine compliance with treatment.

Adrenocortical hyperfunction is a condition where there is an overexpression of products of the adrenal cortex.

When cortisol is overproduced, it is called Cushing's syndrome.

When aldosterone is overproduced, it is called hyperaldosteronism.

Pituitary ACTH hypersecretion (or Cushing disease) is a form of hyperpituitarism characterized by an abnormally high level of ACTH produced by the anterior pituitary. It is one of the causes of Cushing's syndrome. (However, Cushing's syndrome can be caused by many other causes, including exogenous administration.)

Classically, hypercholesterolemia was categorized by lipoprotein electrophoresis and the Fredrickson classification. Newer methods, such as "lipoprotein subclass analysis", have offered significant improvements in understanding the connection with atherosclerosis progression and clinical consequences. If the hypercholesterolemia is hereditary (familial hypercholesterolemia), more often a family history of premature, earlier onset atherosclerosis is found.

Acanthosis nigricans should be distinguished from the casal collar appearing in pellagra.

Acanthosis nigricans is typically diagnosed clinically. A skin biopsy may be needed in unusual cases. If no clear cause is obvious, it may be necessary to search for one. Blood tests, an endoscopy, or X-rays may be required to eliminate the possibility of diabetes or cancer as the cause.

On biopsy, hyperkeratosis, epidermal folding, leukocyte infltration, and melanocyte proliferation may be seen.