by Lisa B. Nachtigall, M.D.
NEPTCC Newsletter Volume 21, Issue 1, Spring/Summer 2014 [PDF version]
A generally healthy 34 year old man with a recent history of hypertension came to medical attention during a June hospitalization in Virginia for “heat exhaustion” and the worst headache of his life following routine military training exercises. He also reported visual disturbance, fever, nausea and vomiting and underwent an MRI of the brain which showed a large pituitary mass measuring 3.2cm x 1.8cm x 2.5cm and abutting the undersurface of the optic chiasm (Figure 1 a and b).
Approximately three weeks later, he was seen at MGH for further work-up and management. Retrospectively, he reported a four year history leading up to the acute episode of carpal tunnel syndrome and enlargement of his brow, hands, and feet requiring increasing sizes of his wedding ring and combat boots. He also noted the development of skin tags on his neck and underarms.
His exam was notable for typical features of acromegaly including a large jaw, coarsening of facial features and broadened nose, frontal bossing, and enlarged hands with thickened metacarpalphalangeal and proximal interphalangeal joints. Visual fields were intact by exam and by formal visual field testing by neuro-ophthalmology. The clinical diagnosis was acromegaly, based on classic findings on history, physical exam and the presence of a pituitary macroadenoma. He was scheduled for surgical resection of what was thought to be a growth hormone secreting pituitary macroadenoma. IGF-I level was obtained on the day of his initial neuroendocrine evaluation and was surprisingly normal at 311 (reference range: 114-492 ng/ml). Other anterior pituitary tests were normal including cortrosyn stimulation, thyroid function tests and prolactin level, with the exception of a low morning testosterone of 209 (270-1070 ng/dl).
The patient opted to defer neurosurgery for three months in order to complete his reserve training and during that interval received three doses of lanreotide 90 mg IM monthly for a presumptive GH secreting macroadenoma. A pre-operative repeat MRI three months later was performed to guide resection and showed involution of the tumor (Figure 1 c and d). There was marked interval decrease in size of heterogeneously enhancing sellar mass to 1.2 cm SI by 1.6 cm RL by 1.1 cm AP. The surgery was cancelled. In the subsequent 12 months and with no further therapy, the patient’s physical features of acromegaly regressed and his hypertension resolved. MRI showed complete involution of the tumor two years later with no additional therapy (Figure 1 e and f). IGF-1 remained normal and random growth hormone was 0.39 (2-6 ng/ml). All of his anterior hormone tests were normal including cortisol > 18mcg/dl, free thyroxine, and testosterone, which had increased into the mid normal range.
In summary, this patient presented with clinical evidence of acromegaly, likely secondary to a pituitary macroadenoma, and hypogonadism and had spontaneous resolution of acromegaly due to a possible apoplectic event (e.g., bleeding and autoinfarction of the adenoma). Gonadal function also spontaneously recovered. In retrospect, the severe headache and “heat exhaustion” just before presentation likely represented apoplexy. It is also possible that the three dose of lanreotide contributed to tumor shrinkage, but of note, IGF-1 was normal before the medication was used.
Spontaneous resolution of acromegaly due to presumed apoplexy, while rare, has been reported in the medical literature in over 25 cases (1-5), beginning in 1986 (6) before wide spread use of pituitary MRI and including case reports that date back to the 19th century, when complete regression of features of acromegaly in the Mexican governor of California Pio Pico was explained by presumed apoplexy. Photographs of Governor Pico from 1873 show no signs of acromegaly compared with 1857, when classic features of acromegaly had been evident (7). In these prior case reports of apoplexy associated with remission of acromegaly, a wide range of precipitating factors were proposed, including anticoagulation (8), cerebral angiography (9), contrast dye (10), diabetes mellitus (3) and thyroid surgery (11). However this is the first case report to my knowledge, in which intensive physical training was associated with the onset of symptoms of apoplexy and presumed regression of acromegaly.
Most cases in the literature were reported before the availability of MRIs (2), or were in patients diagnosed after tumor involution (4), or included patients who underwent surgical intervention despite spontaneously normalized growth hormone after apoplexy (3). Thus, few reports demonstrate complete spontaneous resolution of a macroadenoma by imaging (2, 5). In the patient described here, his decision to postpone surgery provided the opportunity to capture the natural history of his tumor resolution on MRI scans following presumed apoplexy and three doses of medical treatment.
While hypopituitarism has been reported to occur in the majority of patients following apoplexy associated with acromegaly remission (2), this patient has recovered gonadal axis function and maintained normal pituitary function of the other hormone axes. Importantly, he has had no recurrence of his pituitary macroadenoma on MRIs up to three years after the initial presentation. It is possible that the tumor had a dramatic response to three doses of long acting somatostatin analog. However, the medication is unlikely to explain all of his clinical improvement since the IGF-1 was already normal before the somatostatin analog was administered. Additionally, there has been no progression of tumor and no elevation of IGF-1 or GH over three years of follow up. While a period of remission has been reported in a small minority of patients with acromegaly following chronic somatostatin analog treatment for at least 14 months (12-14), it is rare to remain in remission for two years after stopping somatostatin (13) and remission has not been reported after only three doses.
This is an unusual case of acromegaly because most patients require surgery and/or long term medical therapy to control large tumors but this patient had spontaneous regression of the large adenoma and/or after three months of medical therapy. The normal IGF-1 prior to medical therapy with somatostatin analogue suggested that his disease spontaneously improved prior to any therapy. In addition, apoplexy is usually associated with a decrease in pituitary function, and in this patient, gonadal function recovered and other pituitary axes remained normal. He will be monitored carefully for recurrence, but so far is doing very well on no pituitary-related medications and MRI remains stable three years after he experienced the episode of severe headache and exhaustion.