Androgen insensitivity syndrome (AIS), previously referred to as testicular feminization, is an X-linked disorder in which the patients are genotypically male (possessing and X and Y chromosome) and phenotypically female. This disorder is rare, with reported incidences from 1 in 20,000 to 1 in 60,000 live male births, and is the result of a missing gene on the X chromosome that is responsible for the cytoplasmic or nuclear testosterone receptor. In its absence, the gonad, which is a testis, produces normal amounts of testosterone; however, the end tissues are unable to respond due to the deficient receptors leading to the external genitalia developing in a female fashion. Anti-mullerian hormone, which is produced by the testis, is normal in these patients, leading to regression of the Mullerian duct. Wolffian duct development, which depends on testosterone, does not occur as the ducts lack the receptors.
The cumulative effect is a genotypic male with normal external female genitalia (without pubic or axillary hair), no menses, normal breast development, short or absent vagina, no internal sex organs, and the presence of testis. Frequently, these patients have bilateral inguinal hernias in childhood, and their presence should arouse suspicion of the diagnosis.

Due to the high amount of ADH in their blood, patient is voiding a low volume of urine with high osmolarity and as a result low levels of electrolytes will be present in the serum.

Osteopenia is an early sign of bone weakening that is less severe than osteoporosis.
The numerical result of the bone density test is quantified as a T score. The lower the T score, the lower the bone density. T scores greater than -1.0 are considered normal and indicate healthy bone. T scores between -1.0 and -2.5 indicate osteopenia. T scores lower than -2.5 indicate osteoporosis.
DEXA also provides the patient’s Z-score, which reflects a value compared with that of person matched for age and sex.
Z-score values of -2.0 SD or lower are defined as below the expected range for age and those above -2.0 SD as within the expected range for age.

Hyperthyroid patients show significantly lower resting arterial CO2 tension, tidal volume and significantly higher mean inspiratory flow and pa(O2) than healthy patients. This may of course lead to misdiagnosis of patients with hyperthyroidism as having hyperventilation syndrome.

The empty boxes indicate that the patient has run out of his medication.
Chronic administration of high doses of glucocorticoids (GCs) (e.g., prednisone or prednisolone) and also other hormones such as oestrogens, progestins, androgens and growth hormone induce varying degrees of tolerance, resulting in a progressively decreased response to the effect of the drug, followed by dependence and rarely addiction.
The glucocorticoid withdrawal syndrome (GWS) has been considered a withdrawal reaction due to established physical dependence on supraphysiological GC levels.
The severity of GWS depends on the genetics and developmental history of the patient, on his environment, and on the phase and degree of dependence the patient has reached. Its management should include a temporary increase in the dose of GCs followed by gradual, slow tapering to a maintenance dose.

In Conn’s syndrome hypokalaemia and hypertension are present due to high levels of aldosterone with normal to high sodium levels. In this disease, the patient presents with hypertension and feelings of tiredness or fatigue.

Thiamine deficiency is very common with alcoholism. It manifests by Wernicke-Korsakoff encephalopathy. The patient is usually agitated, with an abnormal gait and amnesia.

This patient is most likely suffering from diabetes mellitus. Diagnosis of DM involves checking for elevated blood glucose levels (hyperglycaemia).

Treatment with fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations.
Evidence from studies is available to implicate 5 major mechanisms underlying the above-mentioned modulation of lipoprotein phenotypes by fibrates:
1. Induction of lipoprotein lipolysis.
2. Induction of hepatic fatty acid (FA) uptake and reduction of hepatic triglyceride production.
3. Increased removal of LDL particles. Fibrate treatment results in the formation of LDL with a higher affinity for the LDL receptor, which is thus catabolized more rapidly.
4. Reduction in neutral lipid (cholesteryl ester and triglyceride) exchange between VLDL and HDL may result from decreased plasma levels of TRL.
5. Increase in HDL production and stimulation of reverse cholesterol transport. Fibrates increase the production of apoA-I and apoA-II in the liver, which may contribute to the increase of plasma HDL concentrations and a more efficient reverse cholesterol transport.

Rotterdam criteria for the diagnosis of polycystic ovary syndrome:
Two of the following three criteria are required:
1. Oligo/anovulation
2. Hyperandrogenism
– Clinical (hirsutism or less commonly male pattern alopecia) or
– Biochemical (raised FAI or free testosterone)
3. Polycystic ovaries on ultrasound
Other aetiologies must be excluded such as congenital adrenal hyperplasia, androgen-secreting tumours, Cushing syndrome, thyroid dysfunction and hyperprolactinaemia.
Cushing’s is excluded because there would have been marked obesity, hypertension and other related features.

The patient has a non-functioning pituitary tumour as her hormone profile is normal.
Non-functioning pituitary tumours are relatively common. A large number of these tumours are incidentally found pituitary microadenomas (<1 cm) and are usually of no clinical importance.

A diabetic patient is a patient with depressed immunity. It is not uncommon to develop abscesses. Diabetic patients have a defected cellular innate immunity. On the other hand, bacteria become much more virulent in a high glucose environment in the interstitium.

Carcinoid tumours are of neuroendocrine origin and derived from primitive stem cells in the gut wall, especially the appendix. They can be seen in other organs, including the lungs, mediastinum, thymus, liver, bile ducts, pancreas, bronchus, ovaries, prostate, and kidneys. While carcinoid tumours tend to grow slowly, they have the potential to metastasise.
Signs and symptoms seen in larger tumours may include the following:
– Periodic abdominal pain: Most common presentation for a small intestinal carcinoid; often associated with malignant carcinoid syndrome.
– Cutaneous flushing: Early and frequent (94%) symptom; typically affects head and neck.
– Diarrhoea and malabsorption (84%): Watery, frothy, or bulky stools, gastrointestinal (GI) bleed or steatorrhea; may or may not be associated with abdominal pain, flushing, and cramps.
– Cardiac manifestations (60%): Valvular heart lesions, fibrosis of the endocardium; may lead to heart failure with tachycardia and hypertension.
– Wheezing or asthma-like syndrome (25%): Due to bronchial constriction; some tremors are relatively indolent and result in chronic symptoms such as cough and dyspnoea.
– Pellagra with scale-like skin lesions, diarrhoea and mental disturbances.
– Carcinoid crisis can be the most serious symptom of the carcinoid tumours and life-threatening. It can occur suddenly or after stress, including chemotherapy and anaesthesia.

Primary aldosteronism now is considered one of the more common causes of secondary hypertension (HTN).
Individuals with primary aldosteronism may present with hypokalaemia metabolic alkalosis; however, as many as 38% of patients with primary aldosteronism may be normokalaemia at presentation.
Routine laboratory studies can show hypernatremia, hypokalaemia, and metabolic alkalosis resulting from the action of aldosterone on the renal distal convoluted tubule (DCT) (i.e., enhancing sodium reabsorption and potassium and hydrogen ion excretion).
Plasma aldosterone/plasma renin activity ratio is used for screening because it is fairly constant over many physiologic conditions.

The patient is clinically free, so Cushing diseases can be exclude.

In patients with polycystic ovarian syndrome (PCOS), FSH levels are within the reference range or low. Luteinizing hormone (LH) levels are elevated for Tanner stage, sex, and age. The LH-to-FSH ratio is usually greater than 3.

Women with PCOS have abnormalities in the metabolism of androgens and oestrogen and in the control of androgen production. PCOS can result from abnormal function of the hypothalamic-pituitary-ovarian (HPO) axis.
The major features of PCOS include menstrual dysfunction, anovulation, and signs of hyperandrogenism. Other signs and symptoms of PCOS may include the following:
– Hirsutism
– Infertility
– Obesity and metabolic syndrome
– Diabetes
– Obstructive sleep apnoea

Androgen excess can be tested by measuring total and free testosterone levels or a free androgen index. An elevated free testosterone level is a sensitive indicator of androgen excess. Other androgens, such as dehydroepiandrosterone sulphate (DHEA-S), may be normal or slightly above the normal range in patients with polycystic ovarian syndrome (PCOS). Levels of sex hormone-binding globulin (SHBG) are usually low in patients with PCOS.

Some women with PCOS have insulin resistance and an abnormal lipid profile (cholesterol >200 mg/dL; LDL >160 mg/dL). Approximately one-third of women with PCOS who are overweight have impaired glucose tolerance or type 2 diabetes mellitus by 30 years of age.

The patient’s age and symptoms suggest Grave’s disease with thyroid-associated ophthalmopathy. In Grave’s disease, weight loss is noticed regardless of normal eating habits of the patient. Palpitations are also typical and may be confused with a panic attack. Proptosis is usually bilateral, but unilateral is also possible.

The patient has hyperthyroidism and its most common cause is Grave’s Disease.
Grave’s Disease is an autoimmune disease due to circulating autoantibodies known as TSH receptor stimulating autoantibodies or Thyroid-stimulating immunoglobulins (TSIs) that bind to and activate thyrotropin receptors, causing the thyroid gland to grow and the thyroid follicles to increase the synthesis of thyroid hormone.

For type 2 diabetics, biguanides are the treatment of choice.

Transient congenital hypothyroidism can be due to: iodine deficiency or excess, maternal consumption of goitrogens or antithyroid medications during pregnancy, transplacental passage of TSH receptor-blocking antibodies, and neonatal very low birth weight and prematurity

Subacute thyroiditis (De Quervain’s thyroiditis) is a self-limiting thyroid condition presenting with three clinical courses of hyperthyroidism, hypothyroidism, and return to normal thyroid function. In subacute thyroiditis serum thyroglobulin (TG) levels are elevated. ESR is usually greater than 50 mm/h, often exceeding 100 mm/h. Radio-iodine uptake is low or nil. Antithyroperoxidase antibodies are associated with autoimmune thyroiditis

Classically, pheochromocytoma manifests with the following 4 characteristics:
– Headaches
– Palpitations
– Sweating
– Severe hypertension

The Endocrine Society, the American Association for Clinical Chemistry, and the European Society of Endocrinology have released clinical practice guidelines for the diagnosis and management of pheochromocytoma.
Biochemical testing via measurement of plasma free metanephrines or urinary fractionated metanephrines should be performed in patients suspected of having pheochromocytoma.

Catecholamines produced by pheochromocytomas are metabolized within chromaffin cells. Norepinephrine is metabolized to normetanephrine and epinephrine is metabolized to metanephrine. Because this process occurs within the tumour, independently of catecholamine release, pheochromocytomas are best diagnosed by measurement of these metabolites rather than by measurement of the parent catecholamines.

Dopamine (DA) holds a predominant role in the regulation of prolactin (PRL) secretion. Through a direct effect on anterior pituitary lactotrophs, DA inhibits the basally high-secretory tone of the cell. It accomplishes this by binding to D2 receptors expressed on the cell membrane of the lactotroph, activation of which results in a reduction of PRL exocytosis and gene expression by a variety of intracellular signalling mechanisms.

Acromegaly occurs due to excessive action of insulin-like growth factor I (IGF-I) after the growth plate cartilage fuses in adulthood.
It can be an insidious disease. Symptoms, which may precede diagnosis by several years, can be divided into the following groups:
1. Symptoms due to local mass effects of an intracranial tumour
Tumour damage to the pituitary stalk may cause hyperprolactinemia (Increased blood prolactin levels associated with galactorrhoea) due to loss of inhibitory regulation of prolactin secretion by the hypothalamus
2. Symptoms due to excess of GH/IGF-I including:
– Hyperhidrosis (Not hypohidrosis)
– Arthritis
– Peripheral Neuropathies e.g. Carpal Tunnel Syndrome

Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 hr) of dilute urine (< 300 mOsm/kg). It has the following 2 major forms:
Central (neurogenic, pituitary, or neurohypophyseal) DI, characterized by decreased secretion of antidiuretic hormone (ADH; also referred to as arginine vasopressin [AVP])
Nephrogenic DI, characterized by decreased ability to concentrate urine because of resistance to ADH action in the kidney.
The boy most probably has nephrogenic diabetes insidious (DI) not central DI so he is not responding to the ADH treatment.

Impaired glucose tolerance means that blood glucose is raised beyond normal levels, but not high enough to warrant a diabetes diagnosis. With impaired glucose tolerance you face a much greater risk of developing diabetes and cardiovascular disease. Impaired glucose tolerance is defined as 2-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol) on the 75-g oral glucose tolerance test, and impaired fasting glucose is defined as glucose levels of 100 to 125 mg per dL (5.6 to 6.9 mmol per L) in fasting patients.

Klinefelter’s syndrome: The low follicle-stimulating hormone (FSH) and luteinising hormone (LH), together with the low testosterone, suggests a hypogonadotropic hypogonadism. We know that there is no mental retardation, and we are told that physical examination is normal and sense of smell would usually not be tested. Consequently a diagnosis of Kallman’s is suggested. We are not told of a family history of growth delay, thus this is unlikely to be constitutional delay. The thyroid-stimulating hormone (TSH) is normal, making hypothyroidism unlikely and this together with the normal prolactin make hypopituitarism most unlikely.

Three classes of medications are appropriate for the management of major triglyceride elevations: fibric acid derivatives, niacin, and omega-3 fatty acids.

Fibrate is used as a first-line agent for reduction of triglycerides in patients at risk for triglyceride-induced pancreatitis.

High-dose niacin (vitamin B-3) (1500 or more mg/d) decreases triglyceride levels by at least 40% and can raise HDL cholesterol levels by 40% or more. Niacin also reliably and significantly lowers LDL cholesterol levels, which the other major triglyceride-lowering medications do not.

Omega-3 fatty acids are attractive because of their low risk of major adverse effects or interaction with other medications. At high doses (>4 g/d), triglycerides are reduced.

The boy has an increased BMI which implies he is overweight. Possible trauma to his pancreas might have led to a diabetes-like condition, induced by damage to the beta cells. Fasting blood glucose should be measured as a follow-up strategy to see if the damage is reversible or irreversible and to conclude if the glycosuria is related to his metabolic profile or to his accident.

Hypercalcemia is the most important finding in all types of malignancies. In myeloma it is especially caused by osteoclast activating factors which increase bone turnover.