1. ENDOCRINE CASE STUDIES
Dr SUNIL ZACHARIAH
Consultant Endocrinologist
Spire Gatwick Park and ESH

2. 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

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

4. Presentation is usually 3-4 months postpartum
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

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

6. 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

7. 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

8. 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 2nd sample

9. 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

10. 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

11. 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

12. Case 4 50 year old man Ventricular tachycardia with poor LV function
Controlled on Amiodarone
FT4 50
FT3 7
TSH<0.01

13. 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

14. 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 mg/kg for 3-6 weeks
Management of tachyarrhythmia's: beta blockers if not in CCF
?total thyroidectomy (not radioiodine)

15. 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

16. 24hr Urinary collections
6/3/98
8/3/98
11/3/98
VMA
(5-35)
154
225
192
Normetanephrine
(0.1 – 1.3)
34.8
59.5
54.9
Metanephrine
0.4
0.6
0.7
3-methoxytyranine
(0.1 – 2.0)
4.8
5.6
6,5

17. L.L. CT Scan 1998

18. L.L. MIGB Scan 1998

19. Management of Phaeochromocytoma
Commenced on alpha and beta blockade
Referred for surgery

22. 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

23. INCIDENCE Rare tumours
Accounting for <0.1% of causes of hypertension
Can be fatal if undiagnosed

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

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

26. CLINICAL FEATURES Sustained or episodic hypertension
Sweating and heat intolerance(80%)
Headache(65%)
Palpitations(65%)
Abdominal pain
Constipation

27. COMPLICATIONS CVS: LVF, dilated cardiomyopathy Resp: Pulmonary oedema
Neuro: Cerebrovascular, hypertensive encephalopathy

28. Who should be screened? Family history of MEN, VHL, Neurofibromatosis
Paroxysmal symptoms
Young hypertensive
Patient developing HT crisis during GA
Unexplained heart failure

29. 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

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

31. 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

32. 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

33. 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

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

35. 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
Insulin (mU/L)
Insulin (mU/L) 40 40 *
DISCUSSION
The β-cell secretory response to glucose ingestion, as measured by increases in plasma insulin, was reduced in patients with type 2 diabetes.
Patients with diabetes exhibited a greater β-cell secretory response than control subjects, as indicated by higher insulin secretion levels, during the 180-minute course of intravenous glucose infusion.
BACKGROUND
Differences in insulin response to oral and intravenous glucose administration, which are attributed to factors other than glucose itself, describe the incretin effect; the incretin effect appears to be reduced in patients with type 2 diabetes. Measured insulin and C-peptide responses to a 50 g oral glucose load and an isoglycaemic intravenous infusion. Additionally, an attempt was made to correlate incretin effects to GIP responses.
Insulin measurements are shown here.
Plasma insulin responses were studied for 14 patients with type 2 diabetes in this study and 8 metabolically healthy control subjects.
Nauck MA, et al. Diabetologia 1986;29:46–52 * 20 20 30 60 90
120
150
180 30 60 90
120
150
180
Time (min)
Time (min)
*P ≤.05 compared with respective value after oral load.
Nauck MA, et al. Diabetologia 1986;29:46–52.

36. Incretins and glycaemic control
Ingestion of food
Glucose dependent
Insulin
from beta cells (GLP-1 and GIP)
Beta cells
Insulin increases peripheral glucose uptake
GI tract
Active GLP-1 and GIP
Release of incretin gut hormones
Pancreas
Blood glucose control
Glucagon
from alpha cells (GLP-1) Glucose dependent
Alpha cells
Increased insulin and decreased glucagon reduce hepatic glucose output
DPP-4 enzyme rapidly degrades incretins
Adapted from 7. Drucker DJ. Cell Metab. 2006;3:153– Miller S, St Onge EL. Ann Pharmacother 2006;40:
Drucker DJ. The biology of incretin hormones. Cell Metabolism 2006;3:
Miller S, St Onge EL. Sitagliptin: A dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Ann Pharmacother 2006;40:

37. CASE STUDY-7
88 year old lady
Diarrhoea
Abdominal pain
Weight loss

38. Extensive Investigations for Chronic Diarrhoea(5 years)
PAST MEDICAL HISTORY
Extensive Investigations for Chronic Diarrhoea(5 years)
Diverticular disease
Hypothyroidism
Hypertension
Ischemic Heart Disease
Hysterectomy

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

40. INVESTIGATIONS Hb: 12.9 Bilirubin: 5 WBC: 14.5 ALT: 61
MCV: Alk PO4:
Platelets: Albumin:
Sodium: GammaGT: 533
Potassium: TSH:
Urea: Ft4:
Creatinine: T3:
CRP: Calcium:

41. Urine analysis: NAD
Stool Culture, toxins and microscopy: Negative

42. 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

43. Discussion with patient and family Options discussed
PATIENT PROGRESS
Discussion with patient and family
Options discussed
Patient not keen on further invasive tests
Agreed for CT scan

44. 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

46. TUMOUR MARKERS
CEA: 4.9 (0-15)
CA-125: 55 (0-35)
CA 19-9: 64 (0-27)

47. PROGRESS Diarrhoea persisting
General condition of patient, however good
History reviewed with patient: Feeling flushed for many months
Could this be Carcinoid?

48. 24 hour 5 HIAA requested
Laboratory reluctant
Result: 672 (Normal<31)
Diagnosis of Carcinoid syndrome made
Referral to Oncology and Endocrine team made

49. TREATMENT
Octreotide injections started
Discharged with District Nurse input and Oncology follow up

50. EPIDEMIOLOGY
Annual incidence: 1/ population
Mean age: years
Males=Females
Increased risk of developing other carcinoma’s

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

52. SITE OF OCCURENCE Small Intestine: 39% Appendix: 26% Rectum: 15%
Lungs: %
Rest of GIT: %
Liver: %

53. CLINICAL PRESENTATION
Diarrhoea: %
Flushing: %
Int Obstruction: %
Heart disease: %
Wheezing: %
Carcinoid crisis
Precipitating factors

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

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

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

58. 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%

59. 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

60. Had started growing at a rapid pace since the age of 12 (0
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

61. No headache or visual symptoms
Normal pubertal development
2nd tallest in his class!!!!!!
Enjoys sports and other activities at school, but is troubled by knee pain
Developmental milestones were normal

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

64. IGF nmol/L (30-90)

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

67. Oral GTT Time Glucose GH 0 4.5 109 20 - - 30 4.8 665 60 7.0 367

69. 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

70. 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

71. 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

72. Treatment Transphenoidal surgery is the first line of treatment
Medical therapy