8.2.23 acromegaly BSMS.ppt

Anterior Pituitary Disorders: Acromegaly and Hypopituitarism Dr Jonathan Golding Specialist Registrar in Diabetes and Endocrinology Clinical Research Fellow University Hospitals Sussex [email protected] Learning outcome To understand the presentation, clinical features and management of a...

Anterior Pituitary Disorders: Acromegaly and Hypopituitarism Dr Jonathan Golding Specialist Registrar in Diabetes and Endocrinology Clinical Research Fellow University Hospitals Sussex [email protected] Learning outcome To understand the presentation, clinical features and management of anterior pituitary disorders such as acromegaly, including psychological aspects of endocrine disease. Topics Acromegaly (presentation and diagnosis). Overview of treatment options (surgical, medical, radiotherapy). Hypopituitarism and hormone replacement therapy What are the consequences of a pituitary tumour? • Gland too big – Presses on adjacent structures • Excess hormone secretion • Deficient Hormone secretion – Pressure on normal cells from tumour – Post Surgery or Radiotherapy Pituitary gland - recap Pituitary gland - recap How do we tackle a Pituitary Problem? • • • Take the History Examine the patient Do relevant special investigations The pituitary MDT • • • • • • • • Biochemist Endocrine nurse specialist Endocrinologist Histopathologist MDT co-ordinator Neuro-oncologist Neuro-radiologist Neuro-surgeons • The Person with the problem How do we tackle a Pituitary Problem? • Discuss management with – The MDT – The Person with the problem • Decide on best Personalised treatment • • • • Surgery Radiotherapy Medication Watch & Wait Key features of history • • • • • Presenting complaint History of presenting complaint Family History Past medical and drug history Systematic enquiry – Weight gain / loss – Energy levels – Vision – Periods Case 1 • 40 year old woman presents with visual disturbance, progressive over 1 year • No other symptoms or sign of endocrine disease Is the Pituitary Tumour affecting Vision? Bitemporal Hemianopia Visual defects in pituitary disease • Pituitary gland sits in bony sella turcica, so when enlarges is often forced upwards • This puts pressure on optic chiasm which sits just above pituitary gland • Compression causes bitemporal hemianopia • All patients with pituitary lesions should have visual fields screened MRI scan Pituitary hormones All pituitary hormones were tested and found to be normal including: Prolactin 9am cortisol Thyroid function IGF-1 Periods normal Case 1 – pituitary MDT Attended combined Pituitary Clinic to discuss Surgery Decision made for trans-sphenoidal hypophysectomy KS Post op Post Op MRI Potential hormone problems following hypophysectomy • Any of the pituitary hormones can become deficient following pituitary surgery • Important to follow patients up and check hormone levels • Particularly important are cortisol and monitoring for cranial diabetes insipidus (DI) in initial post-op period Case 1 - Post Op Progress • ADH – Polyuria due to Diabetes Insipidus • Treated with DDAVP (synthetic vasopressin) • Thyroid axis – Free T4 5.5 (12 -22) • Treated with levo-Thyroxine • Adrenal axis – Poor cortisol response to short synacthen test – Continue Hydrocortisone Case 1 - Post Op Progress • Gonadal axis – Oestrogen deficiency – Can be treated with hormone replacement therapy • Growth hormone – GHRH arginine stimulation test done as still scoring low on quality of life assessment – No Growth hormone response – Treat with Growth Hormone subcutaneously daily Case 1 - Post Op Progress • Visual fields normal • Follow up MRIs - no change • Annual Clinic visits – Medical discussion – Biochemical Testing – Discussion with the specialist nurse Summary of learning from Case 1 • Pituitary tumours can compress optic chiasm and cause bitemporal hemianopia – ensure visual fields assessed • Hormone deficiencies can occur as a complication of pituitary tumours or their treatment - ensure all hormones are checked and ask about polyuria to screen for cranial DI Case 2 • • • • 63, presents to Cardiolgist Short of Breath on exertion Ankle swelling Examination – Signs of cardiac Failure – Ejection Fraction 27% on ECHO Case 2 - examination The following pictures are demonstrative and do not necessarily relate to the same patient Please use for private study only and do not reproduce Skin Tags in Acromegaly Increases risk of colon cancer* Acromegaly An excess of growth hormone produced by the pituitary gland Caused by a pituitary adenoma secreting growth hormone Acromegaly – clinical manifestations Soft tissue Bone / joints Cardiovasc ular Respiratory Endocrine Gastrointestinal Increased skin thickness Enlargment of bones / hands / feet Biventricular hypertrophy Sleep apnoea Insulin resistance and type 2 diabetes Colonic polyps Skin tags Increased jaw size (prognatism) Heart failure Macroglossia (tongue enlargement ) Multi-nodular goitre Increased risk of bowel cancer Acanthosis nigracans Prominence of the brow Hypertensio n Hyperparathyroidism Widely spaced teeth (diastema) Hyperhidros is Carpal tunnel syndrome Osteoarthritis Osteoporosis Dyslipidaemia Acromegaly - investigations Growth hormone levels fluctuate through the day so measurement not that helpful Insulin like growth factor (IGF-1) is produced in the liver in response to GH – its levels are more stable. If IGF-1 is raised, oral glucose tolerance test (OGTT) with growth hormone can confirm diagnosis. Normally GH should suppress to <1mcg/L in response to glucose load Case 2 - PMH • Bite problems – Reviewed by dentist • Carpal tunnel syndrome – Reviewed by orthopedic surgeon • Irregular menstrual bleeding – Reviewed by Gynecologist • Loud snoring – Reviewed by ENT Case 2 -Glucose tolerance test with GH Time (mins) Glucose (mmol/L) GH (mcg/L) 0 5.5 24.0 30 6.5 18.8 60 5.1 18.8 90 7.5 16.4 120 8.7 14.4 IGF-1 = 124 nmol/l (14.2 - 36.9) Could there be too much / little of any other hormone? MEN-1 / co-secretion? Ensure all other pituitary hormones are checked – in this case normal Calcium checked and was normal Remember to also check prolactin… • Prolactin release is inhibited by dopamine • Cabergoline (dopamine agonist) can inhibit prolactin release and shrink prolactinomas • Prolactinomas can be treated medically and avert the need for surgery Initial MRI Pituitary Further workup • Vision – Visual fields (normal) • Cardiac – ECG (left ventricular hypertrophy) – Echocardiogram (reduced ejection fraction) • Lung Function /Sleep study – Obstructive sleep apnoea • Colonoscopy normal ( done if > 40 years age) Discussed at Pituitary MDT Decision made for surgery with transphenoidal hypophysectomy Post op - Discharge from Hospital • Hydrocortisone replacement • Information / education – Sick day rules • Form to check Na+ in 1 week – to exclude crania DI • Pituitary clinic appointment Initial post op - MRI Pituitary Post Op MRI • Empty sella • No Chiasmal compression • Some residual tumour seen in cavernous sinus Post op MRI Post Op Tests • Growth Hormone – IgF1 = 59 nmol/l (< 32.9) – OGTT with GH 12.9  7.8 mcg/L • Thyroid – Free T4 = 11.2 pmol/l ( 12-22) • Start Thyroxine • Adrenal – Short Synacthen Test • 423  631 nmol/l (normal) • Stop Hydrocortisone • ADH – Thirst normal, sodium normal • Prolactin – Normal • Gonadal – Periods normal, LH/FSH normal Do we need to normalise the Growth Hormone ? Other options for management of acromegaly • Further Surgery • Medications – Dopamine Agonist – Long acting Somatostatin analogue • Radiotherapy • GH receptor antagonist – Pegvisomant Medical targets for acromegaly Dopamine agonists can be trialled to see if inhibitory effect works Somatostatin analogues will inhibit GH release Pegvisomant is a growth hormone receptor antagonist Case 2 - continued In this case no safe target was identified for further surgery Discussed in Pituitary MDT and radiotherapy agreed as next best step Case 2 – subsequent tests • IGF1 remained high after radiotherapy • Treated with Octreotide LAR 20 mg/ month (somatostatin analogue) • Octreotide has now been stopped as IGF1 came down to the normal range Summary of learning from Case 2 • Acromegaly is caused by growth hormone excess and has effects on multiple systems • OGTT with growth hormone is diagnostic test • 1st line management is surgery • Other treatment options include radiotherapy, dopamine agonists or pegvisomant Psychological aspects of pituitary disease Pituitary disorders can have a profound impact on people’s lives. Themes were explored in following reference: Norman A, Jackson S, Ferrario H, McBride P. Hidden disability: a study of the psychosocial impact of living with pituitary conditions. Br J Nurs. 2022 Jun 9; 31(11):590-597 I have summarised the key themes from this paper on following slides Physical and cognitive effects • • • Lethargy sleep disturbance memory / cognitive impacts Lots of these symptoms are considered nonspecific and often patients go for years with misdiagnosed problems. Perhaps labelled as “depression” or “chronic fatigue” The emotional burden • People can struggle with the burden of treatment • Knowing that their hydrocortisone is “essential for life” and can worry if they miss a dose by mistake Appearance distress • Acromegaly can change appearance considerably which can have impacts on selfesteem • Weight gain can become an issue if thyroid replacement is not quite right Social isolation • Issues with returning to employment can be complex especially with fatigue and the possible need for surgery • This can have an economic impact on individuals • Relationships can be affected and often there is a lack of understanding from friends etc as not many know what the pituitary gland does Learning outcome To understand the presentation, clinical features and management of anterior pituitary disorders such as acromegaly, including psychological aspects of endocrine disease. Topics Acromegaly (presentation and diagnosis). Overview of treatment options (surgical, medical, radiotherapy). Hypopituitarism and hormone replacement therapy Questions