A 54-year-old woman was noted on a routine visit to her ophthalmologist to have bi-temporal hemianopia. She had reported difficulty with reading, but had not noted peripheral vision loss. Her medical history included atrial fibrillation, hypertension, cardiomyopathy, and sleep apnea. On review of symptoms, she reported hirsutism, feeling ‘hot’, palpitations, and diaphoresis.
Q. Define Hirsutism ?
Hirsutism is defined as excessive male pattern of hair growth. It is quantified by Ferriman Gallwey score. Score of >8 /36 is considered as Hirsutism in premenopausal women. Score of 8-15 is mild hirsutism and score >15 is considered as moderate to severe hirsutism.
Q. Should hirsutism be extensively evaluated in post menopausal women ?
Hirsutism is common post-menopausal women. Mild hirsutism per se in post-menopausal women donot require evaluation. However, presence of symptoms of virilization requires evaluation. Virilizing symptoms include
1. Deepening of voice
3. Male pattern baldness
4. Anabolic appearance
Q. What are pathological causes of hirsutism in post-menopausal women ?
1. Obesity associated hyperandrogenism
2. Ovarian hyperthecosis
3. Cushing’s syndrome
5. Adrenal or Ovarian androgenic tumors
6. Classical congenital adrenal hyperplasia (late presentation)
Q. From the history in this case, what is the possible diagnosis ?
Presence of bitemporal hemianopia give a strong suspicion of a pituitary tumor. Other symptoms suggest possibility of either Prolactin (Prolactinoma) , growth hormone (Acromegaly) or ACTH secreting pituitary tumor (Because of presence of Hirsutism with bitemporal hemianopia)
Q. What are differential diagnosis of Bitemporal hemianopia ?
1. Pituitary macroadenoma
3. Suprasellar Meningioma
4. Optic nerve or hypothalamic glioma
5. Rathke’s cleft cyst
6. Aneurysm of anterior communicating artery
Physical examination revealed an obese woman with a BMI of 44, hirsutism, a moon-shaped face, and supraclavicular fullness. She had no goiter or dysthyroid eye disease. She had no overt features of acromegaly such as coarse facial features or broad fingers.
Q. Which clinical features of Cushing’s syndrome has high discriminatory value for diagnosis in Adults ?
1. Facial plethora
2. Easy bruisability
3. Reddish purple striae >1 cm
4. Proximal muscle weakness
Q. What are clinical features of Cushing’s syndrome (From head to toe)
1. Facial plethora
3. Moon like face
5. Supraclavicular fullness
6. Dorso cervical fat pad (Buffalo hump)
9. Red purple striae
10. Proximal muscle weakness
11. Thin skin
12. Peripheral edema
Q. What is your diagnosis at end of history and examination ?
I would like to think that we are dealing with Cushing’s disease (Pituitary cause of Cushing’s syndrome). The points in favour are
1. Presence of bitemporal hemianopia
5. Moon like face
6. Supracalvicular fullness
Point against it are
1. Pituitary Cushing’s is more often due to Pituitary microadenoma. Macroadenoma causing Cushing’s is less common
2. No point of high discriminatory value in physical examination to point towards Cushing’s syndrome.
Initial laboratory testing revealed: thyroxine (T4) 11.4 (5.0–11.0 μg/dl), free thyroxine (fT4) 2.1 (0.7–1.8 ng/dl), TSH 2.8 (0.4–5.5 μU/ml), and tri-iodothyronine (T3) 185 (94–170 ng/dl), insulin-like growth factor 1 (IGF1) 747 (87–267 ng/ml) and GH 1.58 ng/m.
Q. What is your interpretation of the lab reports ?
Anterior pituitary functioning tumor with
1. Central hyperthyroidism (High T3 and T4 with inappropriately normal TSH)
2. GH excess (Increase IGF1 with increase of Random GH)
3. Absence of Stalk compression (Prolactin is normal)
4. Absence of Secondary adrenal insufficiency
It seems to be a functioning ‘plurihormonal’ tumor secreting thyroid and GH.
Bi-temporal hemianopia was present, and magnetic resonance imaging (MRI) of the sella revealed a large pituitary macroadenoma measuring 2.3 cm and left cavernous sinus invasion, with suprasellar extension compressing the optic chiasm, principally to the left of midline.
Click here for the MRI Pictures
Q. What is the Hardy staging of this tumor ?
Hardy Grade E because of Cavernous sinus infiltration
Q. What is the final diagnosis ?
1. Central hyperthyroidism with Growth hormone hypersecretion
2. Pituitary macroadenoma (Hardy Grade E) with cavernous sins infiltration, pressure effect on optic chiasma and no stalk compression.
3. No hypopituitarism
Q. What treatment would you consider for this case ?
1. I would consider neurosurgical referral for debulking of the pituitary tumor. Complete excision of the pituitary mass may not be possible because of extension into the cavernous sinus, however since the tumor is functional and optic chiasma is involved , debulking would be the best option.
2. Since the patient has TSH secreting adenoma, studies have shown preoperative treatment with Octreotide is effective and prevents a thyroid storm. Since this patient is also having atrial fibrillation, lowering of Free T4 and T3 would make the surgery safer. . I would also give beta blockers perioperatively.
Q. How would you manage the patient postoperatively ?
FROM CORTISOL POINT OF VIEW
1. Day of surgery – INJ EFFCORLIN 50 MG / 6 HRLY
2. Post op Day 1 – inj Effcorlin – 50 mg TID
3. Post op day 2- T. HISONE – 20 mg (9am), 10 mg(12 noon) , 10 mg (4 pm)
4. Post op Day 3 – T. HISONE 10 mg (9am), 5 mg (12 noon)
5. Post of Day 4-
a. Send 8 am S. Cortisol
b. Pending Cortisol report continue T. HISONE – 10, 5, 5
S. Cortisol- on 4th post op Day
>12.6 ug/dl- Discharge without Hydrocortisone
10.8-12.6 ug/dl – Clinical judgement
<10.8 ug/dl- discharge on hydrocortisone
6. Call patient back after 6 week
a. Ask patient to skip evening dose of HISONE and get done an 8 am Cortisol
b. Cortisol < 3.6 ug/dl- Lifelong HISONE
c. If cortisol > 3.6 ug/dl- Consider Insulin tolerance / Glucagon suppression test
FROM GH POINT OF VIEW
Day 1 post OP – Send GH (8 am)
If GH < 2 ng/ml- suggests long term remission
12 week Post op
1. GH (8am)
a. If GH >1 ng/ml – do OGTT
3. Repeat MRI sella + contrast
1. If IGF1 normal and GH (nadir) < 1 ng/ml – cure (0.4 is more sensitive cut off)
2. If IGF1 is still high but falling- repeat IGF1 after another 12 weeks before considering further management
3. If IGF1 high and GH (nadir) > 1 ug/dl- active disease –reoperation or gamma knife or continued medical therapy
If IGF1 is normal- repeat it annually
FROM THYROID POINT OF VIEW
I would repeat the thyroid function 6 weeks after surgery. Absence of TSH would point towards good chance of remission. Presence of TSH would mean probability of recurrence. I would keep a close watch.
OTHER COMPLICATIONS TO WATCH FOR
A) Diabetes insipidus
B) Thyroid storm
WHAT WAS DONE IN THIS CASE :
In the context of the initial biochemistry indicating a plurihormonal TSH/GH co-secreting pituitary adenoma, pre-operative treatment with methimazole and octreotide was initiated. She proceeded to transsphenoidal resection of the pituitary macroadenoma 2 weeks later, following a reduction in her diaphoresis, hot flashes, and palpitations. At surgery, a sellar and suprasellar tumor was removed; the diaphragma sella was identified, ballotted down into the sellar region with the pulsations of the cerebrospinal fluid when the tumor was removed, and there was no dehiscence of the diaphragm or transgression of it by tumor identified upon careful inspection after tumor resection; it was believed that a gross total resection was effected
Three weeks later, she reported recrudescence of symptoms of hyperthyroidism (diaphoresis and palpitations), with recurrent evidence of biochemical hyperthyroidism and GH excess; methimazole and octreotide were re-introduced and 2 weeks later thyroid function normalized, T4 10.2 (5.0–11.0 μg/dl) and TSH 4.9 (0.4–5.5 μU/ml). Residual adenomatous tissue was present on sellar imaging (Fig. 2A and B); the tumor appeared to have descended from the suprasellar space into the enlarged sella, sitting above and distorting the infundibulum and compressing the normal gland, both of which enhanced briskly. Repeat, extended transsphenoidal surgery was undertaken.
Normalization of thyroid function and GH levels was observed post-operatively and has persisted, with complete resolution of the hyperthyroidism. Post-operative MRI performed 6 weeks after surgery confirmed gross total resection of the intracranial component of the tumor; the infundibulum remained distorted to the right and is well visualized. At most recent follow-up, 3 years after the initial pituitary surgery, she has residual sleep apnea and continues to use ‘C-PAP’ nightly but is otherwise endocrinologically and neurologically normal
Q. How common it to have a second hormone being secreted in a TSH secreting adenoma ?
TSHoma are plurihormonal in 60% cases. GH and Prolactin are often co-secreted.
LEARNING POINTS FROM THIS CASE
1. TSH Secreting adenoma are often plurihormonal and GH and Prolactin are often co-secreated.
2. Preoperative use of Octreotide in TSH recreating adenoma reduces risk of post operative thyroid storm. However thyroid storm is a well known post operative complication in such a case
3. Recurrence is common in plurihormonal TSH adenomas.