A man in his 60s with headache, nausea and vomiting

A man in his 60s was admitted to the Department of Neurology with headache. The headache had onset the previous evening, and developed to maximum intensity in the space of a couple of hours. There was exacerbation on the day of admission, with a gradual increase in pain without the characteristics of a seizure. He described compressive pain at the top of the head radiating towards the eyes on both sides. He had attempted to take ibuprofen at home for the pain, but vomited up the tablets each time. He had vomited a total of five times on the day of admission. The previous three days he had worked outside in the heat a great deal, and eaten and drunk little.

The patient had known coronary disease and had had angioplasty treatment for angina over ten years previously. He had had chronic pain in the pelvis and lower back for several years, and been treated for this at the hospital's Pain Clinic. Ten years previously, an oesophageal ulcer had been found. He had no known allergies, was a non-smoker and had had no previous reactions to drugs. He was taking an angiotensin-converting enzyme inhibitor (ACE inhibitor) (ramipril tablets 5 mg x 2), beta-blocker (metoprolol slow-release tablets 50 mg x 1), statins (atorvastatin tablets 20 mg x 1) and a platelet inhibitor (acetylsalicylic acid tablets 75 mg x 1). He was still working.

On admission the patient complained of headache, was wearing sunglasses and asked for subdued room lighting. He was markedly photophobic but did not have a stiff neck. His blood pressure was 130/88 mm Hg, pulse regular at 56 beats/min, and temperature 37.2 °C. Blood tests showed: leukocytes (LPC) 7.5 · 10⁹/l (3.5–10.0), haemoglobin 14.9 g/dl (13.4–17.0), thrombocytes (TPC) 115 · 10⁹/l (145–390), CRP 0.60 mg/l (0.0–5.0), creatinine 80 µmol/l (60–105), estimated glomular filtration rate (eGFR) > 90 ml/min/1.7 m², troponin T < 10 ng/l (0.00–14), sodium 140 mmol/l (137–145), potassium 3.9 mmol/l (3.5–4.5), albumin-corrected calcium 2.22 mmol/l (2.17–2.53). Findings of neurological examination were normal, with no cranial nerve deficits or motor or sensory deficits in the upper or lower extremities. Donder's test revealed a normal field of vision and no visual disturbances. Head CT was also described as normal. There was no fever or CRP rise indicating infection. The conclusion following the initial examination was that there was little probability of a serious underlying cause of the patient's headache. The patient was admitted to hospital for observation and pain relief.

The day after admission he had persistent severe pain, was still vomiting and failed to keep down either food or medicines taken by mouth. A lumbar puncture was performed and findings were clear, colourless cerebrospinal fluid with LPC 1 · 10⁶/l (0–4) and total protein 0.77 g/l (0.10–0.50). CSF glucose was 2.5 mmol/l (2.5–4.0) and serum glucose 5.1 mmol/l (4.0–6.3), giving a ratio of 0.49. Opening pressure was unfortunately not measured. IgG antibodies against Borrelia burgdorferi were detected in the cerebrospinal fluid, but the test for IgM antibodies was negative. Similarly, there were elevated values of Borrelia burgdorferi IgG in blood (550 % of the detection limit), and negative IgM. The antibody ratio was not consistent with intrathecal antibody production. The polymerase chain reaction (PCR) test was negative for enterovirus, varicella zoster virus and herpes simplex virus types 1 and 2 in the cerebrospinal fluid. Serology was negative for tick-borne encephalitis and consistent with previous infections with the herpes simplex and varicella zoster viruses. On vague suspicion of migraine attacks, pain relief was attempted with subcutaneous sumatriptan. This had no effect.

On the third day following admission he had persistent headache without improvement. On this day he noticed double vision for the first time after being up walking about for a while. The patient was weak.

D-dimer was negative, and ophthalmoscopy did not reveal papillary stasis. There was still no neck stiffness. CT angiography of the venous phase was conducted, and findings were normal.

On the fourth day after admission, abductive palsy of the right eye occurred. Electrolyte status was tested again and revealed that hyponatraemia had developed, with serum sodium 127 mmol/ (137–145) compared with 140 on admission four days earlier. His CRP value had risen to 16. The previous night his headache had worsened, but tramadol provided effective pain relief. A clinical examination revealed bilateral tenderness over the temporal area and eye pain.

There was no known previous rheumatic disease, no joint pain or skin problems mentioned in the patient's history, no tenderness to palpation over the temporal arteries and his pulse was fine. Blood tests showed LPC 4.7 · 10⁹/l (3.5–10.0), sedimentation rate (SR) was 16 mm/hour (2–20), CRP 16 mg/l (0.00–5.0) and TPC 106 · 10⁹/l (145–390). The conclusion was that clinical findings did not indicate classical temporal arteritis, nor was there any basis for other vasculitis disease in the patient's clinical symptoms or history.

The results of the rheumatic tests came later: RF latex test < 20 IU/ml (< 20), anti-cyclic citrullinated peptide antibodies (anti-CCP) U/ml (< 7), negative for antinuclear antibodies (ANA), anti-proteinase-3 antibodies (PR3-ANCA) 2 units (< 20) and myeloperoxidase antibody (MPO-ANCA) 3 units (< 20). As no diagnosis had yet been made, a head MRI was ordered, but owing to a shortage of capacity the scan could not be performed the same day. The new onset hyponatraemia was discussed with the duty internal medicine specialist. There was no known renal disease in the patient's history, and the patient did not use diuretics, but was taking an ACE inhibitor (ramipril, tablets 5 mg x 2). It was assumed that the hyponatraemia had a bearing on the nausea and vomiting.

On the fifth day following admission, the hyponatraemia had worsened to 121 mmol/l (137–145). Serum potassium was 4.0 mmol/l (3.5–4.4) and serum osmolality 254 mmol/l (280–300). His CRP value had risen to 76. There was no definite suspicion of infection. The spot urine test showed osmolality of 890 mosmol/kg (300–900), sodium 159 mmol/l and potassium 32 mmol/l. Clinically, the patient was regarded as normovolaemic.

The neurologist repeated the request for an MRI scan and asked for renewed scrutiny of the pituitary gland on the original head CT images. At the same time, the duty internal medicine specialist was contacted. Hydrocortisone (Solu-Cortef) 100 mg was administered intravenously on suspicion of central hypopituitarism with hypocortisolism, and the patient was given isotonic saline (NaCl 0.9 %). He was moved to the Intermediate Intensive Care Department for closer monitoring of vital parameters and electrolyte imbalances. 100 mg hydrocortisone was also prescribed for intravenous administration every six hours.

Hormone tests for the pituitary axes showed thyroid-stimulating hormone (TSH) 0.35 mIU/l (0.39–4.2), free thyroxine (FT₄) 7.3 pmol/l (11.0–22.0) and free triiodothyronine (FT₃) 2.3 pmol/l (3.1–6.8). This was consistent with central hypothyroidism. The 11 a.m. cortisol test showed low values: 14 nmol/l (ref. (7)-9 a.m.: 220–850 nmol/l, 7–9 p.m.: < 50 % of morning value). The prolactin value was 23 mIU/l (100–400), while follicle-stimulating hormone (FSH) at 5.7 IU/l (1.0–12.0) and luteinising hormone (LH) at 1.6 IU/l (1.0–10.0) were within the normal ranges. The testosterone value was < 1.0 nmol/l (9.0–35.0) and growth hormone was 1.0 µg/l. The set of test results was consistent with hypopituitarism along several axes (Fig. 1).

A repeat scrutiny of the head CT scan carried out on admission revealed a low-attenuation lesion in the pituitary gland (Fig. 2). An emergency head MRI scan showed haemorrhage in a pituitary adenoma with a bulge into the cavernous sinus on the right side and affection of the abducens nerve. There was expansion of the sella turcica with absent right lateral wall and pronounced thinning of the posterior wall, which was consistent with an adenoma that had developed over a long period of time with remodelling of surrounding bone. There were also some non-specific lesions in the white matter. The patient was transferred the same evening to the Department of Neurosurgery at Oslo University Hospital. He underwent surgery the following day, with transsphenoidal resection of the pituitary tumour and haemorrhage.

After the operation, the diplopia receded almost completely, but the patient had permanent hypopituitarism and needed substitution treatment with cortisone, levothyroxine, testosterone and desmopressin.