Loss of gonadal function of any cause. Diagnosis requires testing of sex hormone and gonadotropin levels. This section includes absent or delayed puberty, primary testicular failure, premature ovarian failure, and secondary hypogonadotropic hypogonadism.

Detailed history,including pubertal development,is mandatory in all patients as this may reduce the list of differential diagnoses considerably.

Specific lines of questioning are indicated according to the exact problem, as below.

The list of differential diagnoses will be different in a patient with multiple medical problems or an obvious congenital condition.

Serious systemic illness of any cause is associated with pubertal delay. Specific conditions associated with abnormal pubertal develoment include the intersex disorders, pseudopseudohypoparathyroidism, Cushing's syndrome andcongenital hypothyroidism.

Pubertal delay is defined by theabsence of thelarche by age 13, or menarche by age 16.

Assess thetiming ofpuberty in as much detail as possible: timing of secondary hair development, breast development and menarche in females, increase in testicular and penile volume, early morning erections and voice breaking in males.

Loss of secondary sexual characteristics such as body hair,and aninability to build new muscle mayoccur withgonadotropin deficiency of any cause.

Weight loss may indicate the development of hypopituitarism or hyperthyroidism. Hypogonadotropic hypogonadism may also occur with Cushing's syndrome and in obesity.

Tall stature and a feminine or 'eunucoid' body shape may be associated with absent puberty in males.

Gynaecomastia may indicate gonadotropin deficiency but in the absence of other symptoms other causes should be considered. Gynaecomastia occurring in conjunction with weight loss should alert to the possibility of malignancy and other systemic diseases.

Absent libido occurs with primary hypogonadism.

New onset loss of libido may be associated with hypogonadism though may be multifactorial.

This may indicate sex hormone deficiency.

Differential diagnoses differ between primary and secondary amenorrhoea.

For secondary amenorrhoea or oligomenorrhoea, specifically assess for symptoms ofpolycystic ovarian syndromeas well as hyperprolactinaemia and thyroid dysfunction below.

Previous pregnancies may help define the duration of disease.

Amenorrhoea and breast swelling are signs of early pregnancy which may not be noticed in the oligomenorrhoeic patient.

Post partum haemorrhage leading to Sheehans syndrome as a cause of hypopituitarism is possible if the patient was unable to breast feed and developed secondary amenorrhoea.

Frequency of shaving varies widely but is usually constant within an individual adult.

Loss of early morning erections is usually important though erectile dysfunction is frequently multifactorial. Symptoms of erectile dysfunction may not be forthcoming unless specifically asked about.

These are all causes of gonadal failure, though orchitis is frequently asymptomatic.

Maldescent may be associated with gonadal dysfunction as well as an increased risk of malignancy.

Hyperprolactinaemia of any cause usually causes hypogonadotropic hypogonadism.

Ask about headache, visual disturbance, breast swelling and galactorrhoea.

Hypothyroidism is a common cause ofdelayed puberty.

Also ask whether the patient hasdeveloped increased sweating, palpitations, tremor, weight loss or diarrhoea, as thyrotoxicosis may also cause gynaecomastia andoligomenorrhoea.

Patients presenting with infertility can on rare occasion befound to havehypopituitarism.

Anorexia nervosa and very low BMI of any cause may cause hypothalamic dysfunction.

Soyacontains large amounts of phytoestrogens which may interfere with the hypothalamic-pituitary-gonadal axis and may be associated with reversible gyncecomastia.

Steroids also interact with the hypothalamic-pituitary-gonadal axis and may occasionally be found in preparations thought by the patient to be 'natural' or 'herbal'.

Excessive exercise may lead to hypothalamic dysfunction.

Various agents associated with hypogonadism are listed below (although it is not exhaustive):

Opiates and recreational drugs, for examplediamorphine, morphine sulphate,heroin, marijuana and alcohol.

Steroids, for examplehydrocortisone, beclamethasone, fluticasone interfere with the hypothalamo-pituitary axis.

Exogenous testosterone,for exampleused forfitness, body building or other sports, will alsoenhance estrogen synthesis.

Estrogens and drugs with estrogen-like activity, such as diethylstilbestrol anddigoxin will also cause gynaecomastia in some cases.

Phenytoin alsoenhances estrogen synthesis, as dogonadotropins.

A range of drugs can inhibit testosterone synthesis or action, includingketoconazole, metronidazole, alkylating agents,spironolactone, cimetidine, flutamide, finasteride, and etomidate.

Other agentssuch asmethyldopa,tricyclic antidepressants, diazepam, penicillamine, omeprazole, phenothiazines, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors have all been reported as causing gynaecomastia, though themechanisms underlying this are unclear.

Patients may not report anosmia unless specifically questioned. Kallmanns syndrome is typified by anosmia and hypogonadotropic hypogonadism.

Dental aplasia, cleft palate and dental malalignment requiring orthodontic treatment may not be obvious and are associated with Kallmanns syndrome.

Congenital abnormalities of the urogenital system may occur with Kallmanns and Turners syndromes.

Specifically ask if any family members, for example cousins,have had late or absent puberty,infertility or simply never had children.

Ask also if any family members have had dental or palatal problems, kidney abnormalities or anosmia which might suggest a family history of Kallmanns syndrome.

Congenital hypothyroidism is associated with delayed puberty.

Hypothyroidismis also associated with Turner's syndrome.

These may be associated with Turner's syndrome.

Deafness may be associated with Turner's syndrome.

Patients with Klinefelter's syndrome have an increased incidence of psychiatric problems.

Multiple congenital conditions includeabnormalities of sexual development. Examples includepseudopseudohypoparathyroidism, Russell Silver syndrome, congenital hypothyroidism.

Specificdisorders of sexual development may also be encountered: congenital adrenal hyperplasia,androgen insensitivity syndrome, 5-alpha reductase deficiency, aromatase deficiency, gonadal dysgenesis, Kallmann's syndrome, Turner's syndrome, Klinefelter's syndrome, and other rarer conditions.

Loss of acuity or failing vision at night are worrying features suggesting optic nerve involvement.

Visual field loss, for examplehomonymous hemianopia,is common indicating chiasmal impingement.

It is worth specifically asking whether patients drive and, if so, whether they have had trouble noticing street signs on either side of the road as this may be the first instance in which field loss is noticed.

Assess for red flag symptoms: headaches present on waking, whichworsen on coughing or leaning forward, are more suggestive of increased intracranial pressure.

Headaches or lancing pain across one section of the head or face only are more suggestive of cranial nerve involvement particularly with disease in the cavernous sinus.

Vague symptoms of tiredness, nausea and dizziness may indicate the development of hypopituitarism with ACTH or TSH deficiency.

Diabetes insipidusis uncommon with intrinsic pituitary disease and suggests para sellar pathology.

Pituitary metastases are common and may be the first presentation of malignant disease.

Ask specifically about change of bowel habit, new prostatic symptoms andbreast lumps.

Ask the patient whetherthere has been a change in their weight or body shape. New bruising, redness, acne, hirsuitism, oligomenorrhoea, diabetes, hypertension, depression, osteoporosisor muscle weakness are all associated with Cushing's syndrome, which leads to pubertal delay and hypogonadotropic hypogonadism.

A detailed history of gynaecomastia will help elucidate likely causes.

Peripubertal breast swelling is common and usually requires no treatment. Long standing obesity may be associated with bilateral non-glandular breast swelling. Sudden onset and unilateral gynaecomastia should alert to the possibility of breast cancer.

Sudden onset and unilateral gynaecomastia should alert to the possibility of breast cancer.

Changes in the skin, nipple or unilateral discharge is highly suspicious for breast cancer.

Bilateral galactorrhoea is suggestive of elevated prolatin.

Weight loss and malaise occur with hypopituitarism but may indicate malignancy.

Hyperthyroidism may be associated with gynaecomastia: ask about sweating, palpitations, tremor, weight loss ordiarrhoea.

Hypothyroidism may be associated with delayed puberty.

Cirrhosis, haemachromatosis and congestive cardiac failure are frequently associated with gynaecomastia.

Various agents associated with hypogonadism are listed below (although it is not exhaustive):

Opiates and recreational drugs, for examplediamorphine, morphine sulphate,heroin, marijuana and alcohol.

Steroids, for examplehydrocortisone, beclamethasone, fluticasone interfere with the hypothalamo-pituitary axis.

Exogenous testosterone,for exampleused forfitness, body building or other sports -will alsoenhance estrogen synthesis.

Estrogens and drugs with estrogen-like activity, such as diethylstilbestrol anddigoxin will also cause gynaecomastia in some cases.

Phenytoin alsoenhances estrogen synthesis, as dogonadotropins.

A range of drugs can inhibit testosterone synthesis or action, includingketoconazole, metronidazole, alkylating agents,spironolactone, cimetidine, flutamide, finasteride, and etomidate.

Other agentssuch asmethyldopa,tricyclic antidepressants, diazepam, penicillamine, omeprazole, phenothiazines, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors have all been reported as causing gynaecomastia, though themechanisms underlying this are unclear.

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Hypogonadism diagnosis - history - Endobible

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