Renal carcinoma presenting with adrenocortical insufficiency due to a pituitary metastasis
D J Beckett1,2, R Gama1, J Wright1,2 and G A A Ferns1,2
From the ’ Department of Clinical Biochemistry, Royal Surrey County Hospital, and the 2School of Biological Sciences, University of Surrey, Guildford, Surrey, UK
Additional key phrase: hypopituitarism
Pituitary metastasis from renal clear cell carci- noma is rare. We describe a 56-year-old man who presented with rapidly developing anterior hypopituitarism without visual disturbance, caused by aggressive pituitary metastasis from occult renal clear cell carcinoma.
CASE HISTORY
A 56-year-old man with hypertension and a long-standing migrainous left Horner’s syn- drome presented with a 6-month history of lethargy and vomiting. Initial investigations were unremarkable except for hyponatremia (plasma sodium 124 mmol/L) and a low plasma glucose of 2.6 mmol/L. Basal plasma cortisol was 54 nmol/L, which following an intravenous bolus of 250 µg of synacthen (Novartis, Frimley, UK) rose suboptimally to 184 nmol/L after 30 min (normal response >550 nmol/L), con- firming insufficiency of the pituitary adrenal axis. Thyroid function tests were within the reference range. The patient was ‘diagnosed’ as having Addison’s disease and commenced on hydrocortisone replacement therapy with good effect. Within 2 months he developed loss of libido, hair loss, weight gain and cold intoler- ance. He was therefore referred for evaluation of pituitary function. On physical examination he did not have any features of hypopituitarism, and, in particular, vision was unaffected. Luteinizing hormone releasing hormone (LHRH; Hoechst UK Ltd, Uxbridge, UK) and thyrotrophin releasing hormone (TRH; Cam- bridge Laboratories Ltd, Newcastle-upon-Tyne, UK) stimulation tests were diagnostic of hypogonadotrophic hypogonadism and second- ary hypothyroidism (Table 1). Hydrocortisone therapy was continued and the patient was also
Correspondence: Mr D J Beckett, Department of Clinical Biochemistry, Clinical Pathology, Royal Surrey County Hospital, Guildford, Surrey GU2 5XX, UK.
| Time (mins) | 0 | 30 | 60 |
|---|---|---|---|
| TSH (mU/L) | 0.32 | 1.70 | 1-61 |
| Prolactin (mU/L) | 604 | 853 | 672 |
| LH (IU/L) | <1 | 1 | 1 |
| FSH (1U/L) | 2 | 3 | 3 |
| Thyroxine (60-160) | 59 nmol/L 3.3 pmol/L | ||
| Free T3 (4-3-7-6) | |||
| Testosterone (10-30) | <3 nmol/L | ||
| GH | 1.2 mU/L | ||
| IGF 1 (0-30-1.20) | 0.55 U/ml | ||
Reference ranges are given in parentheses. TSH=Thyr- oid stimulating hormone; FSH=follicle stimulating hormone; GH=growth hormone; IGF=insulin-like growth factor.
started on androgen (restandol) and thyroxine replacement for his anterior pituitary failure.
Magnetic resonance imaging was consistent with a large pituitary tumour extending upwards to the optic chiasm. Visual field perimetry remained normal. The patient subsequently underwent a transphenoidal hypophysectomy, from which he made an unremarkable recovery. Histological analysis of the pituitary tumour suggested the possibility of renal clear cell carcinoma. Subsequent ultrasound and compu- terized tomography scans of the abdomen and chest revealed bilateral renal masses but no other disseminated disease. Biopsy of the renal masses was consistent with renal clear cell carcinoma.
Four months after the initial operation, the patient experienced rapidly diminishing visual acuity and developed a bitemporal hemianopia. He underwent a second transphenoidal hypo- physectomy, complicated by postoperative cra- nial diabetes insipidus, followed by radical pituitary radiotherapy. Further treatment in- cluded interferon gamma therapy for a period of 9 months, resulting in a 50% shrinkage of the
| Case | Known primary | Age/sex | Initial presentation | Hypopituitarism | Visual disturbance | Diabetes insipidus |
|---|---|---|---|---|---|---|
| Anniko et al.6 | Yes | 59/M | Hypopit | Yes | Yes | No |
| James et al.7 | Yes | 75/M | Visual disturbance | No | Yes | No |
| Eick et al .* | Yes | 66/M | Anorexia, fatigue | Yes | Post-op | Not stated |
| Branch et at.9 | Yes | Not stated | Not stated | Not stated | Not stated | Not stated |
| Koshiyama et al.10 | Yes | 57/M | Incidental | Yes | Yes | Yes |
| Post and Kasdon1 | No | 35/F | Visual disturbance | Post-op | Yes | No |
| Buonaguidi et al.12 | No | 53/M | Vision/DI/hypopit | Yes | Yes | Yes |
| Horikoshi et al.13 | No | 51/M | Visual disturbance | Yes | Yes | Post-op |
| Weiss et al.14 | No | 59/M | Impotence/visual disturbance | Yes | Yes | Yes |
| This case | No | 56/M | Adrenal failure | Yes | Post-op | Post-op |
Hypopit=Hypopituitarism; post-op=post-operative; DI=diabetes insipidus.
bilateral renal tumours. Presently he continues on full anterior pituitary replacement therapy, his vision has stabilized and he remains rela- tively asymptomatic.
DISCUSSION
The pituitary gland is an unusual site for metastatic disease, the most common primary tumours being lung, breast and prostate.1.2 Generally, pituitary metastases are present in patients with widespread terminal disease and are often asymptomatic.1 These are usually localized to the posterior pituitary lobe and therefore present most commonly with cranial diabetes insipidus. This is thought to be because the posterior pituitary receives a direct systemic blood supply, whilst the anterior pituitary is served by a portal circulation.3
Renal carcinoma is an exceptionally aggres- sive disease, as 95% of patients have metastatic lesions at post-mortem4 and 21% have intracra- nial deposits.5 Pituitary metastases, however, are rare. Indeed, only nine such cases have been reported (Table 2) and five of these patients were already diagnosed with primary renal carcino- ma.6-14 Unlike the four previously reported cases of pituitary metastasis from occult renal carci- noma, this case was not found to have bitemporal hemianopia on presentation. Pa- tients with pituitary metastases from renal cell carcinoma most commonly develop anterior hypopituitarism (78%) and visual disturbance (78%) but only 33% develop cranial diabetes insipidus.6-14 This suggests that renal carcinoma, unlike other cancers, has a propensity for metastasizing to the anterior rather than poster- ior lobe of the pituitary. The reasons for this
remain unclear. Koshiyama et al.10 suggest that the incidence of diabetes insipidus is under- estimated as its presence can be masked by coexisting hypopituitarism. However, even when on full glucocorticoid replacement, our patient did not develop diabetes insipidus.
In summary, we describe a patient presenting only with symptomatic anterior hypopituitar- ism, without visual disturbance, caused by a pituitary metastasis from an occult renal carcinoma. Although rare, it should be borne in mind that renal carcinoma may present solely as anterior hypopituitarism caused by a pituitary metastasis even if clinical evidence of widespread disease is lacking.
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