Clinical Reasoning: A 41-year-old man with thunderclap headache

A 41-year-old man with a history of low testosterone on androgen therapy presented to the emergency department complaining of acute onset of the worst headache of his life. He reported being well until 6 hours earlier, when he was resting in his hotel room and experienced a thunderclap headache. The headache was initially described as retro-orbital, left-sided, associated with vomiting, and extending to the occiput. It was maximal within moments of onset. There were no associated visual complaints, weakness, numbness, or tingling. On initial examination, he was noted to have preserved mental status. The cranial nerve examination showed intact visual fields, normal extraocular motility, and no evidence of papilledema. Sensorimotor function was intact and symmetric throughout, and his gait was stable and narrow-based. Initial laboratory studies including blood count and metabolic panel were unremarkable. He was administered oxygen via nasal cannula, metoclopramide, and diphenhydramine without improvement.

Thunderclap headache presents multiple diagnostic possibilities, such as subarachnoid hemorrhage, pituitary apoplexy, reversible cerebral vasoconstriction syndrome (RCVS), meningitis, venous sinus thrombosis, and hemorrhagic or ischemic stroke. In this patient who was on androgen replacement therapy, there was concern for venous sinus thrombosis. Given his history of endocrinologic disturbance, there was also concern about disturbance of his hypothalamic–pituitary axis. Specifically, pituitary adenomas can cause disturbance in testosterone, and such tumors are liable to bleed due to their abnormal blood supply. Therefore, pituitary apoplexy was also a strong consideration. The character of the headache and acute onset to maximum severity also raised concern for subarachnoid or intraparenchymal hemorrhage.

Noncontrast head CT was performed and was normal. CSF examination revealed 50 red blood cells (RBC) and 2 white blood cells (WBC) in tube 1 and 3 RBC and 1 WBC in tube 4 without xanthochromia. Glucose was 83 mg/dL and protein was 48 mg/dL. The patient received dexamethasone 10 mg IV, along with 1 L of normal saline and 2 mg morphine IV. The headache remained refractory to multiple medications.

Further history revealed a remote history of IV drug abuse 20 years prior. He had no headache history. He was recently evaluated for sexual dysfunction and started on testosterone gel. However, due to insurance issues, he reported taking this medication inconsistently for several months. Prior workup for testosterone deficiency revealed serum testosterone of 324 (normal 270–1,070 ng/dL) and prolactin 8.4 (normal <20 ng/dL). On further examination, he was noted to have prominent prognathia, frontal bossing, large hands and feet, and macroglossia. He and his wife also noted a recent change in his shoe size and coarsening of his facial appearance. His wife noted that he looked different than he did in photographs from 11 years prior. Further, he was found to have a tattoo of a wedding ring, and reported he could not find one large enough to fit his hands.

Given concern for a pituitary adenoma causing long-standing acromegalic features with new thunderclap headache, urgent MRI brain with and without gadolinium with focus on the pituitary gland was obtained (figures 1–3). This scan showed mild enlargement of the sella turcica along with a 1.1-cm T1-hyperintense lesion demonstrating mixed T2 signal, including low T2 signal components in the pituitary stalk with deviation to the right and mild suprasellar extension without chiasmatic compression. Magnetic resonance venogram demonstrated patent sinuses without thrombus. RCVS was considered as a diagnostic possibility but angiographic imaging was deferred given clinical concern for pituitary adenoma.

Because of these imaging findings, neurosurgery, ophthalmology, and endocrinology were consulted. Endocrinology recommended starting hydrocortisone 50 mg IV every 6 hours to support the hypothalamic–pituitary axis, as well as a workup for a pituitary adenoma including diluted prolactin, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), fT4, T3, luteinizing hormone (LH), follicle-stimulating hormone (FSH), HgbA1c, and serum testosterone. Ophthalmologic examination did not detect any visual field deficits. On dilated funduscopic examination, there was no appreciated disc pallor or edema. Given suspected pituitary hemorrhage, the patient was started on a regimen of IV fluids, metoclopramide, magnesium, and tramadol. This provided some relief and his headache stabilized.

Admission laboratory work ultimately returned notable for IGF-1 elevated at 894 (normal 52–328). Further laboratory studies were within normal limits. Neurosurgery determined that no urgent surgery was indicated. Given the patient’s clinical stability, he was discharged under the care of his wife and went on to establish care at a facility near his home in another metropolitan area. On most recent contact, he reported having undergone trans-sphenoidal resection of his pituitary adenoma and was stable.