clinical endocrinology

CLINICAL ENDOCRINOLOGY(Dr. FAY)

Dr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Introduction to Endocrinoloy Pituitary Disordersa. Hypofunction Disorders-(Pituitary Dwarfism

in Childhood, Panhypopituitarism in adult life)

b. Hyperfunction Disorders-(Pituitary Gigantism in Childhood, Acromegally in Adult life)

c. A case study Adrenal Disordersa. Hypofunction Disorders(Adrenocortical

Insufficiency-Addison’s)b. Hyperfunction Disorders(Cushings)c. Hypocortisolismd. Hypercortisolism Thyroid Disordersa. Hypothyroidismb. Hyperthyroidismc. A Case Study

The Endocrine System


Introduction of Endocrine Diseases Endocrine disorders may be described as either under

secretion(Hypofunction) or over-secretion(Hyperfunction)

Examples Disorder

Oversecretion Cushing’s where a pituitary adenoma secrete ACTH

Undersecretion 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 the target organDr FAY'S Lecture Notes SERRIES- Clinical Endocrinology

Pituitary Dwarfism in Childhood


The lack of growth hormone in childhood results in dwarfism. It may be:

1. Idiopathic2. 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

Panhypopituitarism in Adult Life


The syndrome of panhypopititarism is often due to atrophy or degeneration of the antrior pituitary and is also known as Simmond’s 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


The general effects of adult panhypopituitarism are(1) hypothyroidism, (2) depressed production of glucocorticoidsby the adrenal glands, and (3) suppressedsecretion of the gonadotropic hormones so that sexualfunctions are lost.Thus, the picture is that of a lethargicperson (from lack of thyroid hormones) who is gainingweight (because of lack of fat mobilization by growth,adrenocorticotropic, adrenocortical, and thyroid hormones)and has lost all sexual functions. Except for theabnormal sexual functions, the patient can usually betreated satisfactorily by administering adrenocorticaland thyroid hormones.

Clinical Manifestaations


Lack of GHGradual loss of 20 sex CX’sLoss of pubic auxiliary hairGenital hypoplasiaSecondary amenorrhoea

hypothyroidsmSensitivity to coldAbsence of sweating, depigmentation with

pallor of skinPoor tolerance of infection, tendency to

coma

Summary of the causes of Pituitary Hypofunction


Tumour Infarction Trauma Congenital malformation Infection Hypothalamic disorder

ttiich

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 Klinefelter’s 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


The giant ordinarily has hyperglycemia, and the betacells of the islets of Langerhans in the pancreas areprone to degenerate because they become overactiveowing to the hyperglycemia. Consequently, in about 10per cent of giants, full-blown diabetes mellitus eventuallydevelops.

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 Headaches, visual defects due to pressure defects


Acromegaly. If an acidophilic tumor occurs after adolescence—that is, after the epiphyses of the long boneshave fused with the shafts—the person cannot growtaller, but the bones can become thicker and the softtissues can continue to grow. This condition, shown inFigure 75–8, is known as acromegaly. Enlargement isespecially marked in the bones of the hands and feetand in the membranous bones, including the cranium,nose, bosses on the forehead, supraorbital ridges, lowerjawbone, and portions of the vertebrae, because theirgrowth does not cease at adolescence. Consequently,the lower jaw protrudes forward, sometimes as much ashalf an inch, the forehead slants forward because ofexcess development of the supraorbital ridges, thenose increases to as much as twice normal size, the feetrequire size 14 or larger shoes, and the fingers becomeextremely thickened so that the hands are almost twicenormal size. In addition to these effects, changes in thevertebrae ordinarily cause a hunched back, which isknown clinically as kyphosis. Finally, many soft tissueorgans, such as the tongue, the liver, and especially thekidneys, become greatly enlarged.

Diagnosis of Acromegally


1. X-ray of the pituitary fossa

2. Assessment of heel-pad thickness and assay of GH(the basal serum are elevated)

3. GTT- A normal person will suppress GH in response to glucose load (expected metabolic response) The acromegallic patient’s GH levels do not suppress in response to a high glucose load

4. 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.

5. The Triple function test

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?

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

Causes of Adrenocortical Insufficiency


1. Selective destruction of Adrenal Cortex, Tuberculosis, autoimmune disease

Cx’s : ACTH, adrenal medulla intact2. Total adrenal destruction- Bacterial and

fungal infections, amyloidosis, metastatic carcinoma, TB

Cx’s: ACTH 20 adrenal insufficiency- ACTH deficiency due

to hypo. Pituitary disease Cx’s medulla and zona glomerulosa intact but

atrophy of zona fascilulata an zona reticularis ACTH

Clinical Presentation


Weight loss Abdominal pain Pigmentation Anorexia Lethargy In acute crisis- vomiting, postural

hypotension, nusea and dehydration

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?)

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?

Management


Life-long treatment with HRT 30mg of hydrocortisone daily in divided

doses supplemented with α-fludrocortisone(mineralocorticoid)

Causes of Hypocortisolism


Primary Adrenocortical deficiency Addison’s disease, autoimmune disease, TB Acute adrenal insufficiency- Waterhouse-Fredrichson syndrome Iatrogenic- adrenalectomy Drugs- metyraone, aminoglutemide Cessation of prolonged terapy

Adrenal Enzyme Defects Desmolase, 21α-hydroxylase, 17 α-hydroxylase, 11βhdroxylase

Secondary Causes CRF deficiency, Hypothalamic diseases,ACTH deficiency,

Anti.Pituitary disease Prolonged Steroid therapy

Decrease CBG: 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



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

Diagnosis of Adrenocortical Hyperfunction


Iatrogenic Cushing’s 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 Cushing’s

Failure of the serum cortisol to rise after insulin-induced hypoglycaemia is often a Cx’tic feature of Cushing’s syndrome(Patient’s 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)

Management


Surgical resection where necessay(microadenomas), adrenalectomy

Drug: O’p-DD(adenocorticolytic agent) metyrapone(adrenal C-11 hydroxylase inhibitor). These will suppress cortisol production

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?

Hypothyroidism


Causes Hashimoto’s 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)



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

infertility

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!

Treatment


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

Hypertyroidism


Causes Grave’s Disease, diffuse toxic goitre Toxic multi-nodular goiter Toxic adenoma Exogenously administered iodine and

iodine-containing drugs, e.g. amiodarone X’sive T4 and T3



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

Diagnosis and Treatment


TSHand raised T4, T3

Treatment:Drug admn.- carbimazole Surgery- thyroidectomy Radio-therapy-I131

NB: Regular monitoring

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?

clinical endocrinology

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