Hypothyroidism occurs when there is a deficiency of circulating thyroid hormones. It is commoner in women and is most frequently seen in the age over 60.

Iodine deficiency is the commonest cause of hypothyroidism worldwide.

In developed countries, iodine deficiency is not a problem and autoimmune thyroiditis is the commonest cause.

Glucagon, secreted from the pancreatic islet alpha cells, is considered to be the main catabolic hormone of the body. It raises the concentration of glucose and fat in the bloodstream

There are five different pancreatic islet cells:
Alpha cells (20%) – produce glucagon
Beta cells (70%) – produce insulin and amylin
Delta cells (<10%) – produce somatostatin
Gamma cells (<5%) – produce pancreatic polypeptide
Epsilon cells (<1%) – produce ghrelin

The hormone-active metabolite of vitamin D is 1,25-dihydroxycholecalciferol (commonly known as calcitriol). Its activities raise calcium and phosphate levels in the bloodstream.

The following are the primary effects of 1,25-dihydroxycholecalciferol:

Calcium and phosphate absorption in the small intestine is increased.
Calcium reabsorption in the kidneys is increased.
Increases phosphate reabsorption in the kidneys.
Increases the action of osteoclastic bacteria (increasing calcium and phosphate resorption from bone)
Inhibits the action of 1-alpha-hydroxylase in the kidneys (negative feedback)
Thyroid hormone (parathyroid hormone) Calcium reabsorption in the tubules of the kidneys is increased, but renal phosphate reabsorption is decreased.

A phaeochromocytoma is a rare functional tumour that develops in the adrenal medulla from chromaffin cells. Extra-adrenal paragangliomas (extra-adrenal pheochromocytomas) are tumours that arise in the sympathetic nervous system’s ganglia and are closely connected to extra-adrenal paragangliomas (extra-adrenal pheochromocytomas). Catecholamines are secreted by these tumours, which generate a variety of symptoms and indications associated with sympathetic nervous system hyperactivity.
Hypertension is the most prevalent presenting symptom, which can be continuous or intermittent.

Symptoms are usually intermittent, occurring anywhere from many times a day to occasionally. The symptoms of the condition tend to grow more severe and frequent as the disease progresses.
The ultimate therapy of choice is surgical resection, and if full resection is done without metastases, hypertension is typically cured.

Preoperative medical treatment is critical because it lowers the risk of hypertensive crises during surgery. This is commonly accomplished by combining non-competitive alpha-blockers (such as phenoxybenzamine) with beta-blockers. To allow for blood volume expansion, alpha-blockade should be started at least 7-10 days before surgery. Beta-blockade, which helps to regulate tachycardia and some arrhythmias, can be started after this is accomplished. Hypertensive crises can be triggered if beta-blockade is started too soon.
There should also be genetic counselling, as well as a search for and management of any linked illnesses.

The earliest biochemical change seen in hypothyroidism is an increase in thyroid-stimulating hormone (TSH) levels.

Triiodothyronine (T3) and thyroxine (T4) levels are normal in the early stages.

TBG levels are generally unchanged in primary hypothyroidism.

Parathyroid hormone (PTH) is a polypeptide containing 84 amino acids. It is the principal controller of free calcium in the body.
PTH is synthesised by and released from the chief cells of the four parathyroid glands that are located immediately behind the thyroid gland.
PTH is released in response to the following stimuli:
Decreased plasma calcium concentration
Increased plasma phosphate concentration (indirectly by binding to plasma calcium and reducing the calcium concentration)
PTH release is inhibited by the following factors:
Normal/increased plasma calcium concentration
Hypomagnesaemia
The main actions of PTH are:
Increases plasma calcium concentration
Decreases plasma phosphate concentration
Increases osteoclastic activity (increasing calcium and phosphate resorption from bone)
Increases renal tubular reabsorption of calcium
Decreases renal phosphate reabsorption
Increases renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (via stimulation of 1-alpha hydroxylase)
Increases calcium and phosphate absorption in the small intestine (indirectly via increased 1,25-dihydroxycholecalciferol)

A daily calcium intake of 1,000 to 1,300 mg is advised for adults. Women have a slightly higher calcium need than men and are at a higher risk of developing osteoporosis as they age.

Calcium-rich foods include the following:
Milk, cheese, and butter as dairy products.
Broccoli, spinach, and green beans as green veggies.
Bread, rice, and cereals as whole grain foods.
Sardines, salmon, and other bony fish
Eggs
Nuts
The following foods have the least calcium:
Carrot
Fruits such as kiwis, raspberries, oranges, and papaya
Chicken and pork in meats.

Insulin, a peptide hormone, is produced in the pancreas by the beta-cells of the islets of Langerhans.

The beta-cells first synthesise an inactive precursor called preproinsulin which is converted to proinsulin by signal peptidases, which remove a signal peptide from the N-terminus.

Proinsulin is converted to insulin by the removal of the C-peptide.

Insulin has a short half-life in the circulation of about 5-10 minutes.
Glucagon and parasympathetic stimulation stimulates insulin release.

Insulin is an anabolic hormone. Its actions can be broadly divided into:
Lipid metabolism
Protein metabolism and
Carbohydrate metabolism

For lipid metabolism, insulin:
Stimulates lipogenesis
Inhibits lipolysis by lipase

For carbohydrate metabolism, insulin:
Decreases gluconeogenesis
Stimulates glycolysis
Promotes glucose uptake in muscle and adipose tissue
Promotes glycogen storage
Increases glycogenesis
Decreases glycogenolysis

Protein metabolism:
Stimulates protein synthesis
Accelerates net formation of protein
Stimulates amino acid uptake
Inhibits protein degradation
Inhibits amino acid conversion to glucose

The hormone-active metabolite of vitamin D is 1,25-dihydroxycholecalciferol (commonly known as calcitriol). Its activities raise calcium and phosphate levels in the bloodstream.

In the presence of UVB light, 7-dehydrocholesterol is converted to cholecalciferol in the epidermal layer of the skin, resulting in 1,25-dihydroxycholecalciferol.

Cholecalciferol is then converted to 25-hydroxycholecalciferol in the endoplasmic reticulum of liver hepatocytes by 25-hydroxylase (calcifediol).

Finally, 1-alpha-hydroxylase converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol in the kidney. The key regulatory point in the formation of 1,25-dihydroxycholecalciferol is 1-alpha-hydroxylase, which is induced by parathyroid hormone or hypophosphatemia.

The following are the primary effects of 1,25-dihydroxycholecalciferol:
Calcium and phosphate absorption in the small intestine is increased.
Calcium reabsorption in the kidneys is increased.
Increases phosphate reabsorption in the kidneys.
Increases the action of osteoclastic bacteria (increasing calcium and phosphate resorption from bone)
Inhibits the action of 1-alpha-hydroxylase in the kidneys (negative feedback)

Osteoclasts are bone cell that break down bone tissue.

Parathyroid hormone increases osteoclastic activity.

1,25-dihydroxycholecalciferol increases osteoclastic activity

Calcitonin inhibits osteoclastic activity

Bisphosphonates are osteoclast inhibitors.

A negative feedback mechanism involving the hypothalamic-pituitary-thyroid axis controls the release of T3 and T4 into the bloodstream.

When metabolic rate is low or serum T3 and/or T4 levels are decrease, this triggers the secretion of thyrotropin-releasing hormone (TRH) from the hypothalamus.

TRH goes to the anterior pituitary gland and stimulates secretion of thyroid-stimulating hormone (TSH).

An increased serum level of T3 and T4 inhibits the release of TRH.

PTH is synthesised and released from the chief cells of the four parathyroid glands located behind the thyroid gland.
It is a polypeptide containing 84 amino acids and it controls free calcium in the body.

The following stimuli causes release of PTH:
Increased plasma phosphate concentration
Decreased plasma calcium concentration

PTH release is inhibited by:
Normal or increased plasma calcium concentration
Hypomagnesaemia

The main actions of PTH are:
Increases plasma calcium concentration
Decreases plasma phosphate concentration
Increases osteoclastic activity (increasing calcium and phosphate resorption from bone)
Increases renal tubular reabsorption of calcium
Decreases renal phosphate reabsorption
Increases renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (via stimulation of 1-alpha hydroxylase)
Increases calcium and phosphate absorption in the small intestine (indirectly via increased 1,25-dihydroxycholecalciferol)

Glucagon is a peptide hormone that is produced and secreted by alpha cells of the islets of Langerhans, which are located in the endocrine portion of the pancreas. The main physiological role of glucagon is to stimulate hepatic glucose output, thereby leading to increases in glycaemia. It provides the major counter-regulatory mechanism to insulin in maintaining glucose homeostasis.
Hypoglycaemia is the principal stimulus for the secretion of glucagon but may also be used as an antidote in beta-blocker overdose and in anaphylaxis in patients on beta-blockers that fail to respond to adrenaline.
Glucagon then causes:
Glycogenolysis
Gluconeogenesis
Lipolysis in adipose tissue
The secretion of glucagon is also stimulated by:
Adrenaline
Cholecystokinin
Arginine
Alanine
Acetylcholine
The secretion of glucagon is inhibited by:
Insulin
Somatostatin
Increased free fatty acids
Increased urea production

Glycolysis is the metabolic pathway that converts glucose into pyruvate. The free energy released by this process is used to form ATP and NADH. Glycolysis is inhibited by glucagon, and glycolysis and gluconeogenesis are reciprocally regulated so that when one cell pathway is activated, the other is inactive and vice versa.

Glucagon has a minor effect of enhancing lipolysis in adipose tissue. Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into glycerol and free fatty acids. It makes fatty acids available for oxidation.

When there are excessive levels of aldosterone outside of the renin-angiotensin axis, primary hyperaldosteronism occurs. High renin levels will lead to secondary hyperaldosteronism.

The classical presentation of hyperaldosteronism when symptoms are present include:
Hypokalaemia
Metabolic alkalosis
Hypertension
Normal or slightly raised sodium levels

When there are excessive levels of aldosterone independent of the renin-angiotensin aldosterone axis, primary hyperaldosteronism occurs. Secondary hyperaldosteronism occurs due to high renin levels.

Causes of primary hyperaldosteronism include:
Conn’s syndrome
Adrenal hyperplasia
Adrenal cancer
Familial aldosteronism

Causes of secondary hyperaldosteronism include:
Renal vasoconstriction
Oedematous disorders
Drugs – diuretics
Obstructive renal artery disease

Although patients are usually asymptomatic, when clinical features are present, classically hyperaldosteronism presents with:
Hypokalaemia
Sodium levels can be normal or slightly raised
Hypertension
Metabolic alkalosis
Less common, clinical features are:
Lethargy
Headaches
Intermittent paraesthesia
Polyuria and polydipsia
Muscle weakness (from persistent hypokalaemia)
Tetany and paralysis (rare)

Hypothyroidism is diagnosed using the results of thyroid function tests (TFTs).

In the early stages of the disease, the earliest biochemical change noticed is a rise in thyroid-stimulating hormone (TSH) levels. Free triiodothyronine (T3) and thyroxine (T4) levels are usually normal.

In primary hypothyroidism, the serum TSH level is usually greater than 10 mU/L, and free T4 levels are below the reference range.

Subclinical hypothyroidism is diagnosed when the serum TSH level is above the reference range, and the free T4 levels are within the reference range. The test should, however, be repeated after 3-6 months to exclude transient causes of raised TSH.

In summary, how to interpret TFTs in cases of suspected hypothyroidism is shown below:

Subclinical hypothyroidism
TSH is raised
Free T4 is normal
Free T3 is normal

Primary hypothyroidism
TSH is raised
Free T4 is lowered
Free T3 is lowered or normal

Secondary hypothyroidism
TSH is lowered or normal
Free T4 is lowered
Free T3 is lowered or normal

Primary hyperaldosteronism occurs when there are excessive levels of aldosterone independent of the renin-angiotensin axis. Secondary hyperaldosteronism occurs due to high renin levels.
The causes of primary hyperaldosteronism include:
Adrenal adenoma (Conn’s syndrome) – the most common cause of hyperaldosteronism (,80% of all cases). These are usually unilateral and solitary and are more common in women.
Adrenal hyperplasia – this accounts for ,15% of all cases. Usually, bilateral adrenal hyperplasia (BAH) but can be unilateral rarely. More common in men than women.
Adrenal cancer – a rare diagnosis but essential not to miss
Familial aldosteronism – a rare group of inherited conditions affecting the adrenal glands
The causes of secondary hyperaldosteronism include:
Drugs – diuretics
Obstructive renal artery disease – renal artery stenosis and atheroma
Renal vasoconstriction – occurs in accelerated hypertension
Oedematous disorders – heart failure, cirrhosis and nephrotic syndrome
Patients are often asymptomatic. When clinical features are present, the classically described presentation of hyperaldosteronism is with:
Hypertension
Hypokalaemia
Metabolic alkalosis
Sodium levels can be normal or slightly raised
Other, less common, clinical features include:
Lethargy
Headaches
Muscle weakness (from persistent hypokalaemia)
Polyuria and polydipsia
Intermittent paraesthesia
Tetany and paralysis (rare)
Often the earliest sign of hyperaldosteronism is from aberrant urea and electrolytes showing hypokalaemia and mild hypernatraemia. If the patient is taking diuretics, and the diagnosis is suspected, these should be repeated after the patient has taken off diuretics.
If the diagnosis is suspected, plasma renin and aldosterone levels should be checked. Low renin and high aldosterone levels (with a raised aldosterone: renin ratio) is suggestive of primary aldosteronism.
If the renin: aldosterone ratio is high, then the effect of posture on renin, aldosterone and cortisol can be investigated to provide further information about the underlying cause of primary hyperaldosteronism. Levels should be measured lying at 9 am and standing at noon:
If aldosterone and cortisol levels fall on standing, this is suggestive of an ACTH dependent cause, e.g. adrenal adenoma (Conn’s syndrome)
If aldosterone levels rise and cortisol levels fall on standing, this is suggestive of an angiotensin-II dependent cause, e.g. BAH
Other investigations that can help to distinguish between an adrenal adenoma and adrenal hyperplasia include:
CT scan
MRI scan
Selective adrenal venous sampling

Although Addisonian crisis is a rare illness, it can be fatal if it is misdiagnosed. Hypoglycaemia and shock are the most common symptoms of an Addisonian crisis (tachycardia, peripheral vasoconstriction, hypotension, altered conscious level, and coma).

Other clinical characteristics that may be present are:
Fever
Psychosis
Leg and abdominal pain
Dehydration and vomiting
Convulsions 

Cushing’s syndrome is a group of symptoms and signs brought on by long-term exposure to high amounts of endogenous or exogenous glucocorticoids. Cushing’s syndrome affects about 10-15 persons per million, and it is more common in those who have had a history of obesity, hypertension, or diabetes.

Iatrogenic corticosteroid injection is the most prevalent cause of Cushing’s syndrome. Cushing’s illness is the second most prevalent cause of Cushing’s syndrome. Cushing’s disease is distinct from Cushing’s syndrome in that it refers to a single cause of the illness, a pituitary adenoma that secretes high quantities of ACTH, which raises cortisol levels.

Cushing’s syndrome has several endogenous sources, including:
Cushing’s disease is caused by a pituitary adenoma.
Adrenal adenoma Ectopic corticotropin syndrome, e.g. small cell cancer of the lung
Adrenal carcinoma is a cancer of the adrenal gland.
Hyperplasia of the adrenal glands

Cushing’s syndrome is a group of symptoms and signs brought on by long-term exposure to high amounts of endogenous or exogenous glucocorticoids.

Iatrogenic corticosteroid injection is the most prevalent cause of Cushing’s syndrome.
Cortisol levels fluctuate throughout the day, with the greatest levels occurring around 0900 hours and the lowest occurring at 2400 hrs during sleep. The diurnal swing of cortisol levels is lost in Cushing’s syndrome, and levels are greater throughout the 24-hour period. In the morning, levels may be normal, but they may be high at night-time, when they are generally repressed.

Insulin resistance causes hyperglycaemia, which is a frequent symptom. Insulin resistance can produce acanthosis nigricans in the axilla and around the neck, as well as other skin abnormalities.

In contrast to menorrhagia, elevated testosterone levels are more likely to produce amenorrhoea or oligomenorrhoea. Infertility in women of reproductive age can also be caused by high androgen levels.

A dexamethasone suppression test or a 24-hour urine free cortisol collection can both be used to establish the existence of Cushing’s syndrome.