ENDOCRINE CASE STUDIES

Dr SUNIL ZACHARIAH

Consultant Endocrinologist Spire Gatwick Park and ESH

CASE-1

 23 year old lady  3 months post delivery  Presents with palpitations and loose stools  FT4=32.6 pmol/L  TSH<0.01 mU/L

POSTPARTUM THYROIDITIS

 Incidence varies from 5-11%  More common in women with a family history of hypothyroidism and positive TPO antibodies

CLINICAL FEATURES

 Presentation is usually 3-4 months postpartum  Can be hypothyroidism (40%), hyperthyroidism (40%) or biphasic(20%)  Goiter is present in 50% of patients  To distinguish from Graves disease use thyroid isotope scan and TSH receptor Ab

Pathogenesis

 Destructive autoimmune thyroiditis causing first release of thyroxine and then hypothyroidism as the thyroid reserve is depleted  FNAC shows lymphocytic thyroiditis

Management

     Most patients recover spontaneously without requiring treatment If hyperthyroid use beta blockers rather than antithyroid drugs as the problem is increased release, not synthesis Hypothyroid phase is more likely to require treatment Only 3-4% remain permanently hypothyroid 10-25% will recur in future pregnancies

Case Study-2

 60 year old Type 2 Diabetes  Last HbA1c=8%(64 mmol/mol)  Presents with erectile dysfunction  Not much benefit from Viagra  Testosterone level 8 nmol/L

Hypogonadism in Type 2 Diabetes

 Low testosterone levels are common in people with type 2 diabetes  Effect of testosterone replacement on glycaemic control remains uncertain  If androgen deficiency is suspected then do at least two 9 am testosterone levels. If first sample is low , then check LH, FSH, SHBG, ferritin and prolactin as well in the 2 nd sample

 If testosterone level is between 8 and 12 nmol/L in a symptomatic individual, then a trial of testosterone replacement is warranted  If the man has tried a phosphodiesterase inhibitor without success and has a total testosterone of <12 nmol/L, then a 6 month trial of testosterone is warranted

Case Study 3

 27 year old female  Follicular Cancer of Thyroid  Post surgery, post radioiodine ablation  On Thyroxine replacement (175 mcg)  FT4 19.8

 TSH 0.05

Follow up of thyroid Cancer

 Original diagnosis and treatment  If total thyroidectomy and ablative radioiodine, thyroglobulins usually undetectable if TSH unrecordable  Maintain TSH<0.05

Case 4

 50 year old man  Ventricular tachycardia with poor LV function  Controlled on Amiodarone  FT4 50  FT3 7  TSH<0.01

Amiodarone and Thyroid

 Inhibits thyroidal iodide uptake  Inhibits conversion of T4 to T3 intracellularly  Inhibits T4 entry into cells  Direct T3 antagonism at level of cardiac tissue

Amiodarone induced hyperthyroidism

     2-12% Type 1: Iodine overload in abnormal gland, treat with carbimazole or lithium Type 2: Glandular damage, release of preformed hormones, treat with prednisolone 0.5-1.25 mg/kg for 3-6 weeks Management of tachyarrhythmia's: beta blockers if not in CCF ?total thyroidectomy (not radioiodine)

CASE 5

 32 year old female  BMI=25  Detected to have blood pressure of 210/100 mm Hg  History of palpitations, abdominal discomfort  Investigated for secondary causes of hypertension

24hr Urinary collections

VMA (5-35) Normetanephrine (0.1 – 1.3) Metanephrine (0.1 – 1.3) 3-methoxytyranine (0.1 – 2.0) 6/3/98 154

34.8

0.4

4.8

8/3/98 225

59.5

0.6

5.6

11/3/98 192

54.9

0.7

6,5

L.L. CT Scan 1998

Management of Phaeochromocytoma

 Commenced on alpha and beta blockade  Referred for surgery

DEFINITION

 Phaeochromocytomas are adrenomedullary catecholamine secreting tumours  Paragangliomas are tumours arising from extra adrenal medullary neural crest derivatives, e.g. sympathetic or carotid body, aorticopulmonary, intravagal or parasympathetic

INCIDENCE

 Rare tumours  Accounting for <0.1% of causes of hypertension  Can be fatal if undiagnosed

EPIDEMIOLOGY

 Equal sex distribution  Most commonly in 3 rd and 4 th decades  Majority(90%) are sporadic, 10% are inherited

PATHOPHYSIOLOGY

 Sporadic tumours are usually unilateral and <10 cm diameter  10-20% are malignant  Paragangliomas are more likely to be malignant

CLINICAL FEATURES

 Sustained or episodic hypertension  Sweating and heat intolerance(80%)  Headache(65%)  Palpitations(65%)  Abdominal pain  Constipation

COMPLICATIONS

 CVS: LVF, dilated cardiomyopathy  Resp: Pulmonary oedema  Neuro: Cerebrovascular, hypertensive encephalopathy

Who should be screened?

 Family history of MEN, VHL, Neurofibromatosis  Paroxysmal symptoms  Young hypertensive  Patient developing HT crisis during GA  Unexplained heart failure

INVESTIGATIONS

 24 hour urine collection for catecholamines. Because of episodic nature at least two 24 hour samples  Plasma catecholamines: Limited use because of intermittent secretion. Useful if patient having a crisis  Screening for associated conditions

LOCALIZATION

 MRI or CT scan  MIBG scan: Meta-iodobenzylguanidine is a chromaffin-seeking analogue. Positive in 60 80%.

MANAGEMENT

 Alfa-blockade (Phenoxybenzamine) must be commenced before beta-blockade to avoid precipitating a hypertensive crisis due to unopposed alfa-adrenergic stimulation  Surgical resection (open or laparoscopic)  Malignancy: High dose MIBG therapy, Chemotherapy, Octreotide therapy

Case Study 6

 49 year old 

HGV Driver

 Diagnosed type 2 diabetes 8 years ago  Diet controlled for 1 year  Check’s Blood Glucose once a day (8-13)  On tablets since then  Yearly retinal screening

MEDICATIONS

 Metformin 1 gm bd  Pioglitazone 45 mg od  Gliclazide 80 mg bd  Lipitor 40 mg od  Perindopril 4 mg od  Aspirin 75 mg od

 Hba1c=9.2%  Creatinine=90, GFR=76  ?Next Step

The incretin effect is reduced in patients with type 2 diabetes

Intravenous Glucose Oral Glucose Control subjects Patients with type 2 diabetes 80 80 60 60 40 20

* * * * * * *

0 0 30 60 90 120 150 180 Time (min)

*

P

≤.05 compared with respective value after oral load. Nauck MA, et al.

Diabetologia

1986;29:46 –52.

40 20

* * *

0 0 30 60 90 120 150 180 Time (min)

Incretins and glycaemic control

Ingestion of food GI tract Release of incretin gut hormones Pancreas Glucose dependent



Insulin from beta cells (GLP-1 and GIP) Insulin increases peripheral glucose uptake Beta cells Alpha cells Active GLP-1 and GIP

DPP-4 enzyme rapidly degrades incretins 

Glucagon from alpha cells (GLP-1) Glucose dependent Blood glucose control Increased insulin and decreased glucagon reduce hepatic glucose output

Adapted from 7. Drucker DJ.

Cell Metab

. 2006;3:153 –165. 8. Miller S, St Onge EL.

Ann Pharmacother

2006;40:1336-1343.

CASE STUDY-7

 88 year old lady  Diarrhoea  Abdominal pain  Weight loss

PAST MEDICAL HISTORY

 Extensive Investigations for Chronic Diarrhoea(5 years)  Diverticular disease  Hypothyroidism  Hypertension  Ischemic Heart Disease  Hysterectomy

EXAMINATION

    Mildly dehydrated Hypotensive (94/60 mm Hg) Abdomen: Tenderness in Epigastrium and RUQ CVS: Soft Systolic murmur

INVESTIGATIONS

         Hb: 12.9 Bilirubin: 5 WBC: 14.5 ALT: 61 MCV: 90 Alk PO4: 417 Platelets: 461 Albumin: 42 Sodium: 134 GammaGT: 533 Potassium: 3.6 TSH: 3.3

Urea: 12.6 Ft4: 12 Creatinine: 90 T3: 3.2

CRP: 138 Calcium: 2.4

  Urine analysis: NAD Stool Culture, toxins and microscopy: Negative

IMAGING

 CXR: Normal  Ultrasound Abdomen: Hepatomegaly, with multiple avascular, iso-echoic lesions in both lobes of liver representing metastasis. Primary likely to be ?colorectal or ?pulmonary

PATIENT PROGRESS

 Discussion with patient and family  Options discussed  Patient not keen on further invasive tests  Agreed for CT scan

CT Scan

 No significant lymphadenopathy  No significant lung lesions  Liver is replaced by multiple metastasis in both lobes  Normal pancreas and adrenals  No masses in the ovary or large bowel

TUMOUR MARKERS

 CEA: 4.9 (0-15)  CA-125: 55 (0-35)  CA 19-9: 64 (0-27)

PROGRESS

 Diarrhoea persisting  General condition of patient, however good  History reviewed with patient: Feeling flushed for many months 

Could this be Carcinoid?

 24 hour 5 HIAA requested  Laboratory reluctant  Result: 672 (Normal<31)  Diagnosis of Carcinoid syndrome made  Referral to Oncology and Endocrine team made

TREATMENT

 Octreotide injections started  Discharged with District Nurse input and Oncology follow up

EPIDEMIOLOGY

 Annual incidence: 1/100000 population  Mean age: 50-60 years  Males=Females  Increased risk of developing other carcinoma’s

PATHOLOGY

 Arise from neuroendocrine cells  Characterized histologically by reaction to silver stains and neuroendocrine markers (enolase, chromoganin)

SITE OF OCCURENCE

 Small Intestine: 39%  Appendix: 26%  Rectum: 15%  Lungs: 10%  Rest of GIT: 10%  Liver: 2%

CLINICAL PRESENTATION

 Diarrhoea: 84%  Flushing: 75%  Int Obstruction: 44%  Heart disease: 33%  Wheezing: 15%  Carcinoid crisis  Precipitating factors

BIOCHEMICAL INVESTIGATIONS

 Urinary 5-HIAA: Sensitivity (70%), specificity (100%)  Most sensitive marker is plasma Chromogranin A (100%) but specificity is lower

TUMOUR LOCALIZATION

 Imaging with CT/MRI  Upper and Lower endoscope  Octreotide scan (85%): Positive scan indicates good response to treatment with octreotide

TREATMENT

 Depends on size, location, symptom and growth  Surgery: Removal or debulking  Somatostatin analogues  Hepatic embolization  Chemotherapy/Radiotherapy  Alfa-Interferon

PROGNOSIS

 If detected early, results in complete and permanent cure  Median survival rate improved to 12 years. especially after introduction of somatostatin analogues  If Liver metastasis, 5 year survival is 20-40%

CASE 8

 15 year old boy  GP referral: Concerns expressed by mother regarding height velocity  Already 190 cms [Mother 163 cms and Father 170 cms]  Feet: size 16

 Had started growing at a rapid pace since the age of 12 (0.5 – 1 inch a month)  Sweaty palms  Pain in knees and wrists  Pins needles in both hands

 No headache or visual symptoms  Normal pubertal development  2 nd tallest in his class!!!!!!

 Enjoys sports and other activities at school, but is troubled by knee pain  Developmental milestones were normal

 Initial Ix done by GP revealed - Prolactin 1656 mu/L (86-324) - Testosterone: 1.6 nmol (10-28) FSH, LH within normal range - Normal TFT

 IGF-1 151 nmol/L (30-90)

Examination

     Height 190 cms, weight 86 kg Large hands and feet Prominent ridges on forehead B/L gynaecomastia Visual fields: Normal

Oral GTT

Time Glucose GH 0 4.5 109 20 30 4.8 665 60 7.0 367 90 4.8 196 120 5.5 121

Acromegaly

 Uncommon condition, new case incidence 3-4 per million, mean age of diagnosis 40-45  More than 95% caused by pituitary adenoma, rarely by ectopic GH or GHRH production by malignant tumours  All cause mortality rate is twice that of normal population & is due to cardiac, cerebrovascular, Diabetes & neoplasia (colon cancer) related

Clinical features

     Due to soft tissue enlargement in all organ systems or due to presence of tumour in pituitary fossa Headache and visual field defect Increase in ring/shoe size, hyperhidrosis, coarsening of facial features, prognathism, macroglossia, arthritis Glucose intolerance or diabetes, hypertension, CV disease, cardiomyopathy Increased incidence of Ca colon

Diagnosis

   Oral GTT – Gold standard for diagnosis Imaging – MRI should only be done after a firm biochemical diagnosis, because of high incidence of non-functioning adenomas IGF 1 – Useful in screening and to monitor Rx

Treatment

  Transphenoidal surgery is the first line of treatment Medical therapy