Isaac Matthias, MD1, J. Eric Schmitt, MD, PhD,2
1Department of Internal Medicine, Penn Presbyterian Medical Center, Philadelphia, Pennsylvania, USA
2Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
A 45 year old man with no significant past medical history presented to the ER with one week of generalized headache, accompanied by diffuse myalgias. Labs were significant for serum sodium of 116, with serum osmolality 245, urine osmolality 569, urine sodium 172, TSH 0.75, cortisol 19.9 with ACTH 55.7 (normal 7 – 63). On physical examination he was euvolemic and had normal mentation. Creatinine kinase was increased at 650 (normal range 49 – 397). A diagnosis of SIADH was made and the patient was admitted to the medical ICU for further management.
The patient was restricted to no free water intake. In the first 24 hours of admission urine output increased significantly without intervention, with urine osmolality decreased to 238 and serum sodium increased to 125. 4 micrograms intravenous desmopressin was administered with dramatic decrease in urine output, increase in urine osmolality to 763, and stabilization of serum sodium. 24 hours after desmopressin administration the patient’s urine output and serum sodium began to rise again. The patient’s headache and myalgias resolved with normalization of serum sodium. Due to the patient’s presenting complaint of headache an MRI brain was performed. (Figure 1 – T1 contrast enhanced sagittal MRI. Figure 2 – T1 contrast enhanced coronal MRI.)
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Imaging revealed an 8mm cystic suprasellar mass with mild superior displacement of the optic chiasm and moderate rightward displacement of the pituitary stalk, with an associated 3mm hypodense lesion in the superior pituitary. (Figure 3 – same image from Figure 1, annotated. Figure 4 – same image from figure 2, annotated.)
Pituitary endocrine laboratory workup was unrevealing. Visual field testing revealed slight bitemporal defects. The patient was discharged with outpatient endocrine and neurosurgery followup for possible transphenoidal resection of a presumed benign lesion, possibly a Rathke cleft cyst.
What imaging is appropriate to evaluate a pituitary lesion?
Contrast enhanced, T1 weighted MRI is the preferred imaging modality to evaluate a pituitary lesion. The pituitary enhances with intravenous gadolinium contrast. Compare the images from Figures 1 – 4, which are contrast enhanced, to the non-contrast image from the same series (Figure 5). In the non-contrast image the pituitary is darker, making it difficult to distinguish the suprasellar mass, and the intra-pituitary lesion is no longer visible.
Rhabdomyolysis and myalgias in hyponatremia
Symptoms related to hyponatremia are typically due to cerebral edema, ranging from subtle mental status changes to seizures, coma, and ultimately brain herniation. Hyponatremia can also cause myocyte edema, resulting in myalgias and rhabdomyolysis.1 Our patient’s myalgias and elevated creatine kinase resolved with normalization of serum sodium.
Causes of SIADH
Our patient’s clinical picture was consistent with SIADH, with high urine osmolality and urine sodium, euvolemia on exam, and no history of thiazide use. Reasons for the anterior pituitary to secrete ADH despite euvolemia and low serum sodium include:2
- Drug effects. Commonly implicated drugs include SSRIs, carbamazepine, cyclophosphamide, and MDMA (“ecstasy”).
- Paraneoplastic secretion of ADH (not by the anterior pituitary). Typically due to small cell lung cancer.
- Intracranial pathology, such as a bleed or malignancy.
- Secondary adrenal insufficiency, i.e. failure of the pituitary to release ACTH. Cortisol releasing hormone, secreted by the hypothalamus in response to decreased ACTH, stimulates the pituitary to release both ACTH and ADH.3,4 In our patient with a suprasellar mass this was a consideration, but ACTH and cortisol were both normal.
- The triphasic response…
What is the triphasic response???
The hypothalamic-neurohypophyseal system is composed of neurons originating in the hypothalamus, whose axons run through the pituitary stalk and terminate in the posterior pituitary, where they release ADH and oxytocin. The triphasic response occurs due to injury to these neurons, most commonly from transphenoidal pituitary surgery.5 In the initial phase ADH release is impaired due to neuronal injury, resulting in central diabetes insipidus. After approximately 7 days ADH “leaks” from the damaged neurons, causing a shift to SIADH. Finally, the ADH supply is exhausted, and due to inability of the injured neurons to generate new ADH, diabetes insipidus again occurs. Patients typically experience only one or two of the phases, only rarely progressing to permanent diabetes insipidus.6
In our patient’s case it is likely that spontaneous necrosis or hemorrhage of his suprasellar cystic mass occurred, resulting in headache and injury to the pituitary stalk. Approximately seven days later he experienced an isolated second phase of the triphasic response, resulting in SIADH and hyponatremia. This effect spontaneously resolved, as is common, resulting in suppression of ADH and normalization of his serum sodium.7 Our patient’s serum sodium remained normal on outpatient followup, indicating he did not proceed to the third phase, recurrent diabetes insipidus. Repeat brain MRI two months later showed decrease in the size of his suprasellar mass by half, consistent with resolution of spontaneous necrosis or hemorrhage of the mass.
How is desmopressin used in managing hyponatremia?
In order to avoid osmotic demylenation the serum sodium should be raised by 6 to 8 meq/L in 24 hours.8 This is challenging in patients with appropriately suppressed ADH, as they make large quantities of dilute urine, resulting in a rapid rise in serum sodium. This occurs in patients with psychogenic polydipsia, and in patients whose cause for ADH release has been reversed, such a patient with secondary adrenal insufficiency who is treated with corticosteroids.9 Desmopressin, an ADH analogue, can be given 4 micograms intravenous, resulting in immediate decrease in urine output, increase in urine osmolality, and halting the rise in serum sodium.10 The effect lasts for approximately 24 hours. Patients who have received desmopressin must be counseled and monitored scrupulously to prevent free water intake, a particular risk in psychogenic polydipsia. An increase in urine output and decrease in urine osmolality indicates the desmopressin effect has abated.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the editor of this site.