CASE 22- Not really Non functioning !

Original case by Mana et al

CASE 1

A 51-year-old man was admitted to the hospital because of cranioencephalic trauma following seizures. He had a 10-year history of altered behavior, obesity, depression, sphincter incontinence, and recent visual troubles. Physical examination revealed amaurosis of the right eye with blurred vision in the left eye, signs of hypogonadism, and increased bilateral testicular volume (Prader orchidometer >25 mL). Magnetic resonance imaging (MRI) showed a voluminous lesion in the sellar-suprasellar area with mass effect on the brain and projection toward the floor of the third ventricle (Fig. 2).

Q What are the causes of Macroorchidism ?

  1. Fragile X syndrome
  2. Testicular adrenal rest tumor
  3. Testicular malignancy
  4. FSH secreting pituitary adenoma
  5. Uncontrolled hypothyroidism in a child
  6. Lymphoma
  7. Aromatase deficiency in males

Q What is the Hardy Staging of the Pituitary lesion ?

Hardy Grade E (Parasellar extension into the cavernous sinus)

Q What would you do next ?

I would do an anterior pituitary evaluation

  1. Baseline 8:00 am Cortisol and ACTH stimulation test
  2. IGF1 and GH stimulation test
  3. FSH/LH and testosterone
  4. Free T4 and TSH

Hormone testing showed an FSH level of 517 mIU/mL (normal, 1.5 to 12.4 mIU/mL), luteinizing hormone (LH) level of 2.2 mIU/mL (normal, 1.7 to 8.6 mIU/mL), testosterone level of 1.3 ng/mL (normal, 2.9 to 8.0 ng/mL), prolactin (PRL) level of 21.2 ng/mL (normal, 4.6 to 21.4 ng/mL), thyroid-stimulating hormone (TSH) level of 1.37 mIU/mL (normal, 0.27 to 4.20 mIU/mL), free thyroxine level of 0.8 ng/dL (normal, 0.9 to 1.7 ng/dL), cortisol level of 4.2 μg/dL (normal, 6.2 to 19.4 μg/dL), and insulin-like growth factor 1 (IGF-1) level of 33 ng/mL (normal, 87 to 200 ng/mL).

Q What is your interpretation of the anterior pituitary profile ?

  1. FSH is very high with hypogonadism
  2. Central hypothyroidism
  3. Cortisol is on the lower side, I would do a ACTH stimulation to confirm
  4. IGF1 is low- most likely to have GH deficiency

 

A surgical approach was performed in 2 stages by fronto-pterional access with partial resection of the tumor. Histopathologic examination showed a proliferation of neoplastic cells arranged in nests showing a papillary pattern, consisting of cells with amphophilic and eosinophilic cytoplasm. Immunostaining showed a high percentage (almost 70%) of wide and heterogeneous markers for FSH but was negative for other hormones. Ki-67 was <1%. Final diagnosis was of an FSH-producing gonadotropinoma. Postsurgical hormone assessment showed a decline in FSH to 22.3 mIU/mL.

The patient presented torpid evolution requiring ventricle-peritoneal bypass for hydrocephalus and presented infectious complications needing mechanical ventilatory assistance and hemodynamic support, ending in death.

CASE 2

A 36-year-old woman was referred to our hospital with a history of regular menstrual cycles and 2 pregnancies with normal deliveries. Two years before consultation, she had developed secondary amenorrhea, and multiple bilateral ovarian cysts were detected; she started oral contraceptive treatment, but the cysts continued to increase in number and size. A surgical intervention with wedge resection of both ovaries was performed, but the cysts and amenorrhea persisted after surgery (Fig. 3 A).

Q Was this approach correct ?

Not exactly. The secondary amenorrhea should have been more thoroughly evaluated. I would done a prolactin.

One year later, moderate hyperprolactinemia (69 ng/mL; normal, 4.6 to 21.4 ng/mL) was found, and an MRI showed a pituitary macroadenoma (Fig. 4 A).

Q What would you do next ?

I would do the following

  1. Repeat prolactin with 1:100 dilution
  2. Perform the anterior pituitary profile

Cabergoline 0.5 mg per week induced normalization of PRL, but neither tumor shrinkage nor resolution of amenorrhea was observed.

Q What this approach correct ?

No. The Prolactin was mildly elevated and no consistent with the Pituitary adenoma. It was more likely to be a non-functioning adenoma with stalk compression.

Hormone assessment showed: TSH, 2.6 mIU/mL; thyroxine, 10.3 ng/mL (normal, 4.5 to 12.5 ng/mL); IGF-1, 221 ng/mL (normal, <494 ng/mL); PRL, 66 ng/mL; FSH, 20.2 mIU/mL (normal, <12 mIU/mL); LH, 0.5 mIU/mL (normal, <12.6 mIU/mL); and estradiol, 288 pg/mL (normal, <161 pg/mL)

Q What would be your approach to this patient ?

I would offer pituitary surgery since she is having amenorrhea

Transsphenoidal extirpation of the pituitary adenoma was performed. Immunostaining was positive for PRL and FSH, confirming the diagnosis of an FSH-producing gonadotropinoma. After surgery, the patient recovered regular menstrual cycles. Disappearance of ovarian cysts on ultrasound and almost complete absence of the adenoma on MRI were shown. Blood test showed normalization of PRL (18 ng/mL), FSH (13.1 mIU/mL), LH (10.5 mUI/mL), and estradiol (5.7 pg/mL) values.

DISCUSSION

Q What is the composition of nonfunctioning adenomas ?

They are more likely to be gonadotropinomas as in this case.

Q What are the characteristics of FSH secreting adenomas in males ?

They are generally clinically non-functioning. They sometimes have Macroorchidism.

Q How do they present in women ?

They present with large ovarian cysts.

Q What is the importance of LH in these females ?

Suppression of LH and high FSH goes in favour of FSH secreting pituitary adenoma. This would help differentiate it from Primary ovarian insufficiency and menopause.

 

LEARNING POINTS

  1. FSH secreting pituitary adenomas may present as Macroorchidism in male and bilateral multicystic ovaries in females
  2. Low LH and high FSH in females would help to differentiate it from POI and menopause.

 

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