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Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

CLINICAL ENDOCRINOLOGY (Dr. FAY) Introduction to Endocrinoloy Pituitary Disorders Hypofunction Disorders-(Pituitary Dwarfism in Childhood, Panhypopituitarism in adult life) Hyperfunction Disorders-(Pituitary Gigantism in Childhood, Acromegally in Adult life) A case study Adrenal Disorders Hypofunction Disorders(Adrenocortical Insufficiency-Addisons) Hyperfunction Disorders(Cushings) Hypocortisolism Hypercortisolism Thyroid Disorders Hypothyroidism Hyperthyroidism A Case Study

The Endocrine System

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Introduction of Endocrine Diseases

Endocrine disorders may be described as either under secretion(Hypofunction) or over-secretion(Hyperfunction) Disorder

Examples

Oversecretion Undersecretion

Cushings where a pituitary adenoma secrete ACTH Primary hypothyroidism where the thyroid gland is unable to synthesize T4, T3 despite continuous stimulation of y TSH

Failure of hormone responsiveness

Pseudohypothyroidism where patients become hypocalcaemic despite elevated PTH concentration due to the lack of function receptor a Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology the target organ

Pituitary Dwarfism in Childhood

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The lack of growth hormone in childhood results in dwarfism. It may be: Idiopathic Secondary to tumours in and around the pituitary e.g. craniopharyngioma In the idiopathic type, shortness of stature s first noticed at the age of 2 to 3 years. The body proportions are normal There is usually delay in tooth eruption and bone show retarded growth. As years go by, height remains shorter even when compared to bone age, more so to chronological age The facial features are immature. Muscle bulk is below normal There is also sexual infantilism

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Panhypopituitarism in Adult Life

The syndrome of panhypopititarism is often due to atrophy or degeneration of the antrior pituitary and is also known as Simmonds disease. In some instances the cause of the anterior pituitary involvement ay be due to; Granulomatous lesions Invasion of tumour Surgery or radiation The resulting lack of topic hormone e.g. gonadotropins, corticotropin etc. become manifest in due course
Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

The general effects of adult panhypopituitarism are (1) hypothyroidism, (2) depressed production of glucocorticoids by the adrenal glands, and (3) suppressed secretion of the gonadotropic hormones so that sexual functions are lost.Thus, the picture is that of a lethargic person (from lack of thyroid hormones) who is gaining weight (because of lack of fat mobilization by growth, adrenocorticotropic, adrenocortical, and thyroid hormones) and has lost all sexual functions. Except for the abnormal sexual functions, the patient can usually be treated satisfactorily by administering adrenocortical and thyroid hormones.

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Clinical Manifestaations
Lack of GH Gradual loss of 20 sex CXs Loss of pubic auxiliary hair Genital hypoplasia Secondary amenorrhoea hypothyroidsm Sensitivity to cold Absence of sweating, depigmentation with pallor of skin Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology to coma Poor tolerance of infection, tendency

Summary of the causes of Pituitary Hypofunction Tumour Infarction Trauma Congenital malformation Infection Hypothalamic disorder

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Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Pituitary Hperfunction
Pituitary Gigantism in Childhood

Gigantism results from excessive production of growth hormone in the prepubertal period and this is usually associated with eosinophilic adenoma of the pituitary, CAH, Hyperthyroidism or inherited disorders such as Klinefelters syndrome Tallness can be to the extent of 7 to 9 feet usually with postural defects. Normal pubertal growth is absent. Hands and feet may be very large

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

The giant ordinarily has hyperglycemia, and the beta cells of the islets of Langerhans in the pancreas are prone to degenerate because they become overactive owing to the hyperglycemia. Consequently, in about 10 per cent of giants, full-blown diabetes mellitus eventually develops.

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Acromegally in Adult life

Acromegally results from over-function of the pituitary especially in the production of somatotropin in adult life. The most likely cause is a pituitary adenoma The clinical manifestation are: Overgrowth of endochondral bone and skeletal changes become most marked in acral portions Skin is thickened, coarse and greasy. Increase infolds especially on the forehead gives a bull-dog like appearance Hands and feet become spatulate in appearance Body hair may increase and result in mild hirsutism Protruding jaw (prognathism) Larynx changes result in alteration which become deep and gruffly Sweating Impaired glucose tolerance or DM, Goitre, hypertension, adrenal hyperfunction, gonadal hypofunction Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology Headaches, visual defects due to pressure defects

Acromegaly. If an acidophilic tumor occurs after adolescence that is, after the epiphyses of the long bones have fused with the shaftsthe person cannot grow taller, but the bones can become thicker and the soft tissues can continue to grow. This condition, shown in Figure 758, is known as acromegaly. Enlargement is especially marked in the bones of the hands and feet and in the membranous bones, including the cranium, nose, bosses on the forehead, supraorbital ridges, lower jawbone, and portions of the vertebrae, because their growth does not cease at adolescence. Consequently, the lower jaw protrudes forward, sometimes as much as half an inch, the forehead slants forward because of excess development of the supraorbital ridges, the nose increases to as much as twice normal size, the feet require size 14 or larger shoes, and the fingers become extremely thickened so that the hands are almost twice normal size. In addition to these effects, changes in the vertebrae ordinarily cause a hunched back, which is known clinically as kyphosis. Finally, many soft tissue organs, such as the tongue, the liver, and especially the Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology kidneys, become greatly enlarged.

Diagnosis of Acromegally
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X-ray of the pituitary fossa Assessment of heel-pad thickness and assay of GH(the basal serum are elevated) GTT- A normal person will suppress GH in response to glucose load (expected metabolic response) The acromegallic patients GH levels do not suppress in response to a high glucose load IGF1- Elevated levels of IGF1 in serum confirm the diagnosis of acromegally (insulin-like growth factor) (Growth h stimulates liva to produce IGF-1) there is a normal ve feedback to control this(gh and p..) Adenoma of pituitary does not respond to this. Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology The Triple function test

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

A Case Study

Kofi Taller a 21-year old mason and a native of Anomabo, recently became worried when his friends begun teasing him of his excessive height(1.85metres) and funny limbs. A doctor friend advised him to see an endocrinologist about his condition. He sweats often, has elevated but not extremely elevated high blood pressure. He also complains of intemittent headaches. What is the possible differential diagnosis? How would you investigate this case to arrive at a definitive diagnosis? How would you manage such a patient and why?
Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Adrenal Disorders
Basic Facts Acute adrenal insufficiency is very rare condition with low incidence rate Very fatal if not recognized Simple to manage Patient can lead a normal life once treated
Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Causes of Adrenocortical Insufficiency

Selective destruction of Adrenal Cortex, Tuberculosis, autoimmune disease Cxs : ACTH, adrenal medulla intact Total adrenal destruction- Bacterial and fungal infections, amyloidosis, metastatic carcinoma, TB Cxs: ACTH 20 adrenal insufficiency- ACTH deficiency due to hypo. Pituitary disease Cxs medulla and zona glomerulosa intact but atrophy of zona fascilulata an zona reticularis ACTH
Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

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Clinical Presentation

Weight loss Abdominal pain Pigmentation Anorexia Lethargy In acute crisis- vomiting, postural hypotension, nusea and dehydration

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Biochemical Presentation

Hyponatraemia- due to lack of aldosterone leading to pathological sodium loss by the kidney Absence of cortisol also leads to impairment of water load excretion Hyperkalaemia Elevated serum urea Hypotension Pre-renal uraemia Raised ACTH (Why?)
Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Diagnosis

FACTS TO KNOW Ensure adequate sodium intake whilst investigation proceess Serum aldosterone measurement have no clinical significance in initial diagnosis A single serum cortisol measurement could be misleading The Short Synacten Test: indicates the ability of the adrenal cortex to respond to Synacten (a synthetic analogue of ACTH) Measure baseline plasma cortisol (280-720nmol/L). I.V. admn. Of 0.25mg Synacten Measure the increase in plasma cortisol after 30mins RESULTS:? - In a normal individual the basal value shd be > 225nmol/L and there should be an increment of >200nmol/L and the final conc. Shd be >500nmol/L. Failure to meet this criteria confirms adrenal insufficiency A normal response to the test excludes primary hypofunction An elevated ACTH, confirms primary adrenal failure in a patient with an impaired response response to the Synacten test. Why?
Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Management
Life-long treatment with HRT 30mg of hydrocortisone daily in divided doses supplemented with -fludrocortisone(mineralocorticoid)

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Causes of Hypocortisolism
Primary

Adrenocortical deficiency Addisons disease, autoimmune disease, TB Acute adrenal insufficiency- Waterhouse-Fredrichson syndrome Iatrogenic- adrenalectomy Drugs- metyraone, aminoglutemide Cessation of prolonged terapy Desmolase, 21-hydroxylase, 17 -hydroxylase, 11hdroxylase CRF deficiency, Hypothalamic diseases,ACTH deficiency, Anti.Pituitary disease Prolonged Steroid therapy

Adrenal Enzyme Defects

Secondary Causes

Dr CBG: FAY'S Lecture Notes SERRIESClinical Endocrinology Decrease Nephrotic syndrome, severe liver disease, Androgen therapy

Hyperfunction of the Adrenal Cortex

Causes
Prolonged exposure to cortisol or any other glucocorticoids Pituitary adenoma Ectopic ACTH Adrenal adenoma Adrenal carcinoma Product affected Cortisol Adrenal Adrogens Aldosterone Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Clinical Presentation

Baldness and facial hirsutism in females Buffalo hump Increased abdominal striae Hypertension Skin thining Brusability Poor wound healing Muscle weakness Osteoporosis Moon face, Plethoric cheeks
Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Diagnosis of Adrenocortical Hyperfunction

Iatrogenic Cushings should be diagnosed from the patient history and clinical examination The steroid may have been taken orally, inhaled or applied topically Cortisol secreted in excess by the adrenal cortex, will rapidly exceed the CBG threshold Urinary free cortisol in 24-H collection (High), or screening for the urinary cortisol:creatinine ratio (often high) Circadian rhythm of cortisol (cf to normal subjects), evening sample often lower than morning but no so in the AdHyp patient Failure to suppress serum cortisol ff 1mg overnight intake of Dexamethasone implies Cushings Failure of the serum cortisol to rise after insulin-induced hypoglycaemia is often a Cxtic feature of Cushings syndrome(Patients with cortisol over-production will be resistant and a std. 0.15unis insulin/Kg body weight will not be adequate to achieve hypoglycaemic state, a higher dose may be required)
Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Management

Surgical resection where necessay(microadenomas), adrenalectomy Drug: Op-DD(adenocorticolytic agent) metyrapone(adrenal C-11 hydroxylase inhibitor). These will suppress cortisol production

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Case Study

A 28-year newly wedded lady, Mrs Rudith Bompata was referred for investigation of oligomenorrhoea, hirsutism, weight gain and easy brusability. She was normotensive with excessive adipose tissue on the trunk area. Radiology revealed minimal osteoporosis. The pituitary fossa was within normal limits. She had extremely elevated free urinary cortisol(2200nmol/24H (4-250nmol) What possible differential diagnosis will you give and why? What further investigation would you pursue to reach a definitive diagnosis? How would you manage such a patient?
Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Hypothyroidism
Causes Hashimotos diseases (autoimmune), leads to the destruction of the thyroid gland Irradiation(I131 therapy) Drugs: lithium Panhypopitutarism leading to TSH deficiency Congenital defects e.g. defects in T3 and T4 biosynthesis

Severe iodine deficiency (IDD, Ghana)

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Clinical Presentation

Lethargy and tiredness Cold intolerance Weight gain Dryness and coarse skin/hair Anaemia, constipation, dementia, infertility

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Diagnosis

Demonstration of TSH conc. is usually diagnostic of primary hypothyroidism-Why? Secondary hypothyroidism, failure of the pituitary to secretion TSH, is much less common. Isolated pituitary deficiency of TSH is rare but the H-P-T axis may happen as a result of any pituitary disease or damage Find out TRH Test!

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Treatment

HRT(T4)- very inexpensive, easily available in pure form but need for regular monitoring to assess adequacy of treatment

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Hypertyroidism
Causes Graves Disease, diffuse toxic goitre Toxic multi-nodular goiter Toxic adenoma Exogenously administered iodine and iodinecontaining drugs, e.g. amiodarone Xsive T4 and T3

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Clinical Presentation

Wt Loss Sweating and heat intolerance Fatigue Palpitation- tachycardia Muscle weakness Diarrhoea Goitre Eyelid retraction infertility

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Diagnosis and Treatment

TSHand raised T4, T3 Treatment:Drug admn.- carbimazole Surgery- thyroidectomy Radio-therapy-I131 NB: Regular monitoring

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Case Study

Akosua Dora a 45-year old yam-seller from Kintampo present with multi-nodular goitre. Her BMI is 15 but she has a very good appetite. What preliminary investigations may be necessary to establish the cause of her condition? What is the most likely diagnosis and why? Would you suggest a primary or secondary cause and why? How will her conditioned be managed and what are the precautions?
Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology