Pituitary problems

Sahaja Gopu

• Pituitary gland – endocrine gland which is pea sized and it sits in pituitary fossa, which is situated in the sphenoid bone in the middle cranial fossa at the base of the brain.

• Pituitary gland has two components – anterior pituitary or adenohypophysis and posterior pituitary or neurohypophysis.

Hormones secreted Hypothalamus Pituitary gland

GHRH- Growth Hormone Releasing Hormone

GH – Growth Hormone

CRH – Corticotrophin Releasing Hormone ACTH - Induces cortisol release from the adrenal cortex

GnRH – Gonadotrophin Releasing Hormone

FSH and LH

Prolactin

TRH –Thyrotophin Releasing Hormone TSH – Induces thyroid hormone production by the thyroid

Vasopressin – released by posterior pituitary

Stimulates conservationof water by the kidneys

Pituitary tumours

• Tumours are almost always benign and cause effects include – hyper/hypo pituitarism and local effects.

• Different types of tumours -• Non-functioning adenomas• Prolactinoma• GH-secreting tumours• ACTH-secreting tumours• Thyroid-stimulating hormone-secreting• Leutinising hormone/follicle-stimulating hormone (LH/FSH)-

secreting tumours. • Metabolic risk factors such as hypertension, hyperlipidaemia and

glucose intolerance are enhanced in many patients with pituitary disease and should be vigorously addressed

Local effects

• Headache – Usually retro-orbital or bi temporal, worse on waking. Sudden catastrophic headaches may be result in acute pituitary failure which is rare medical emergency.

• Visual field defects –Bitemporal hemianopia is classic but any defect can occur.

• Ocular nerve palsy – squint.• Disorders of thirst, appetite, temperature regulation may

occur if extended onto hypothalamus.

Hyper and hypo pituitarism

• ACTH producing tumour presents as cushings syndrome.• GH secreting tumour – Acromegaly and Gigantism in children.

Slowly progressive.• Prolactima – microadenoma are common.• Hypopituitarism tends to occur in the following order of leutinising

hormone , growth hormone, thyroid-stimulating hormone , and lastly adrenocorticotrophic hormone and follicle-stimulating hormone. Therefore the presentation in adults tends to be infertility, oligo/amenorhea, decreased libido and erectile dysfunction. Deficiency of LH and GH may result in decreased muscle bulk, decreased body hair, central obesity and small, soft testes. In children,it commonly presents with delayed puberty or impairment of growth.

Prolactinoma

• Benign tumour• Prolactin production can be stimulated by various

factors: dopamine receptor antagonists, thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide (VIP) or epidermal growth factor, and by suckling an infant ; inhibited by dopamine.

• Classification :Microadenomas: <10 mm.• Macroadenomas: >10 mm.• Giant pituitary adenomas: >40 mm.• Malignant prolactinomas -very rare

Causes of hyperprolactinaemia

• Physiological – pregnancy, puerparium, stress, non fasting sample• Intracranial causes:• 1.Prolactinomas: Microprolactinomas -MCC about 90%,

Macroprolactinomas 10%(>10 mm size),Pituitary or hypothalamic tumour compressing the pituitary stalk, eg craniopharygioma.

• 2.Head injury• Endocrine causes• Hypothyroidism (due to increased synthesis of TRH).• Cushing's syndrome.• Chronic renal failure• Severe liver disease• Polycystic ovarian syndrome• Drugs Prolactinoma can also occur in about 20% of patients with multiple

endocrine neoplasia type 1

Drugs causing hyperprolactinaemia

• Dopamine receptor antagonists, eg domperidone, metoclopramide, neuroleptics.• Dopamine-depleting agents, eg methyldopa.• Antidepressants, e.g tricyclic antidepressants, monoamine-oxidase inhibitors,

serotonin reuptake inhibitors.• Verapamil.• Opiates.• Protease inhibitors.• Benzofibrate.• Omeprazole.• H2-receptor antagonists.• Oestrogens, anti-androgens.• Cyproheptadine.• Cocaine.

Prolactinoma

• In women -Infertility, Amenorhea, oligomenorhea, galactorhea, reduced libido.

• In men symptoms are subtle which include reduced libido,erectile dysfunction and reduced beard growth.

• Headache.• Visual disturbances (classically, a bitemporal hemianopia (lateral

visual fields) or upper temporal quadrantanopia).• Cranial nerve palsies• Symptoms and signs of hypopituitarism• Investigations – exclude pregnancy, TFTs, basal prolactin level.

MRI and visual field testing.

Treatment

• Indications for treatment are: effects of tumour size and hyperprolactinaemia.

• Treatment -medical with dopamine agonists like cabergoline or bromocriptine. Others include surgery+/- radiotherapy.

• Cardiac valvopathy and pleural and pericardial fibrosis are serious side effects of cabergoline.

• During pregnancy there is a small risk of tumour enlargement, particularly with macroadenomas and if treatment is required, bromocriptine and cabergoline appear to be safe during pregnancy.

Hypopituitarism

• Presentation varies from asymptomatic to acute pituitary failure with acute collapse and coma, depending on the aetiology, rapidity of onset, and predominant hormones involved.

• May present with endocrine dysfunction:– Adrenocorticotrophic hormone (ACTH) deficiency:

• Chronic: fatigue, pallor, anorexia, weight loss• Acute: weakness, dizziness, nausea, vomiting, circulatory collapse, fever, shock• Children: delayed puberty, failure to thrive• Hypoglycaemia, hypotension, anaemia,

lymphocytosis, eosinophilia,hyponatraemia– Thyroid-stimulating hormone (TSH) deficiency:

• Tiredness, cold intolerance, constipation, hair loss, dry skin, hoarseness, cognitive slowing

• Weight gain, bradycardia, hypotension• Children: retarded development, growth retardation

Hypopituitarism

– Gonadotropin deficiency:• Women: oligomenorrhoea, loss of libido,

dyspareunia, infertility, osteoporosis• Men: loss of libido, impaired sexual function, mood impairment,

loss of facial, scrotal, and body hair; decreased muscle mass, osteoporosis, anaemia

• Children: delayed puberty– Growth hormone deficiency:

• Decreased muscle mass and strength, visceral obesity, fatigue, decreased quality of life, impairment of attention and memory

• Dyslipidaemia, premature atherosclerosis• Children: growth retardation

– Antidiuretic hormone deficiency:• Polyuria, polydipsia• Decreased urine osmolality, hypernatraemia

– May also present with features attributable to the underlying cause:• Space-occupying lesion: headaches or visual field deficits• Large lesions involving the hypothalamus: polydipsia

and inappropriate secretion of antidiuretic hormone

Cushing’s disease

• The most specific signs of Cushing’s disease are proximal myopathy , facial plethora, easy bruising and reddish purple striae greater than 1 cm wide and neuropsychiatric problems.

• The best screening test for the presence of hypercortisolaemia remains sequential 24-hour urinary-free cortisol measurements. Late night salivary cortisols are increasingly available.

• Metyrapone 500 mg – 4 g daily in divided doses reliably but reversibly inhibits adrenal cortisol synthesis and secretion.Other modes include surgery

• There remains a significant, persistent and unpredictable tendency to relapse that affects almost one-third of patients by 10 years

• Sheehans syndrome – pan hypopituitarism

Case

• A previously fit 36-year-old man presented with a 2 year history of enlarged hands and feet. In particular, he had noticed that he needed an increased shoe size. He was otherwise well, with no other symptoms. There was no past medical history or family history of note. On examination, the only significant finding was that the man’s hands appeared disproportionately large and broad and rather ‘spade-like’ in nature. Otherwise, examination was entirely normal.

Acromegaly

• Prolonged excessive secretion of growth hormone.• MC cause is pituitary adenoma- 99%• Mean age of diagnosis is 40-45yrs and delay in diagnosis is

common.• Common in both sexes and all races.• It is slow growing tumour and changes in appearance may not

be noticed easily hence comparing with old photographs may be useful.

Signs and symptoms

Changes in appearance • Coarse, oily skin—women may also have mild hirsutism • Change in facial features—enlarged suprorbital ridges, wide nose,

prognathism • Increase in foot and hand size (a bigger shoe size is needed or rings

no longer fit) • Skin tags • Increase in teeth spacing • Macroglossia Pressure effects • Headache• Visual field defects

Other non specific • Tiredness and lethargy • Deepening of voice • Sweating (50–80%) • Paraesthesiae • Musculoskeletal pain • Menstrual irregularities and/or galactorrhoea (due to

associated hyperprolactinaemia) • Visceral hypertrophy—liver, kidneys, prostate, heart, thyroid

(multinodular go

Conditions associated

• Respiratory - Sleep apnoea (20–80%)• Cardiovascular• Hypertension (40%)• Heart failure• Cardiomyopathy• Arrhythmia• Metabolic• Diabetes mellitus (19–56%)• Lipid disturbances• Hypercalciuria• Musculoskeletal• Osteoarthritis of the back and weight-bearing joints (20–50%)• Carpal tunnel syndrome (20–52%)• Malignancy• Gastrointestinal—colonic polyps and colonic cancer• Other—possible increase in lung, thyroid and breast

Diagnosis and treatment

• In primary care, if a diagnosis of acromegaly is suspected, check a random growth hormone and IGF-1 level and if abnormal refer for specialist advice.

• Options – 1.surgery [hypophysectomy] • 2. medical with somatostatin analogues ie Octreotide• 3. other dopamine agonists with cabergoline • Follow up – lifelong with specialist.• All patients with acromegaly should be offered regular

colonoscopic screening for bowel cancer starting at the age of 40 years.

Akt questions• A 28 year old woman comes to see you. She feels tired all the time,

and has been seeing the health-visitor who suspects postnatal depression. She had a post-partum haemorrhage following the delivery of her first child two years ago. She has put on a stone in weight, is cold and amenorrhoeic. She is unhappy, but not depressed. She desperately wants to conceive, and has been trying for a year. You check a subfertility screen. She is not ovulating. Free T4 and TSH are both very low, as is Prolactin, LH and FSH. Which one of the following is the most likely diagnosis?

a ) Cushing’s syndromeb ) Hypothyroidismc ) Kallman’s syndromed ) Polycystic ovarian syndromee ) Sheehan’s syndrome

• A 42-year-old man presents to his GP feeling generally unwell. For the past three months he has been experiencing daily frontal headaches which have not been helped by regular paracetamol. He has also noticed some unusual symptoms such as his wedding ring no longer fitting, his shoe size apparently increasing and a small amount of milky discharge from both nipples. On examination his blood pressure is 168/96 mmHg. What is the most likely diagnosis?

• A 45-year-old man with a history of depression and gastro-oesophageal reflux disease presents to his GP due to a milky discharge from his nipples. The following blood results are obtained:Prolactin 700 mu/lWhich one of his medications is most likely to be responsible?

• A Metoclopromide• B cimetidine• C Flouexetine

• An 18-year-old male presents to his GP concerned about delayed pubertal development, despite being 1.77m tall. On examination he has scant pubic hair and reduced testicular volume. The following blood results are obtained:Testosterone6.7 nmol/l (9 - 30)LH3 .1 mu/l (3 - 10)FSH5.7 mu/l (3 - 10)What is the most likely diagnosis?

• A kallmann’s syndrome• B Klienefelter’s syndrome• C primary testicular failure• D Testicular feminisation syndrome

• Klinefelter's - LH & FSH raisedKallman's - LH & FSH low-normal

kallman’s syndrome

• Kallman's syndrome is a recognised cause of delayed puberty secondary to hypogonadotrophic hypogonadism. It is usually inherited as an X-linked recessive trait.

• Features include :delayed puberty• hypogonadism, cryptorchidism• anosmia• sex hormone levels are low• LH, FSH levels are inappropriately low/normal• patients are typically of normal or above average height

• 52-year-old man presents to his GP as he is concerned about a discharge from his nipples. Which one of the following drugs is most likely to be responsible?A Ranitidine

• B Isoniazid• C Spironolactone• D Chlorpromazine