The influence of status epilepticus on adeno-pituitary hormone secretion in man : with special reference to prolactin

Epileptic seizures as well as antiepileptic drugs (AED) may interfere with the hypothalamic pituitary axis (HPA) and have neuroendocrine effects. A transient increase of prolactin (PRL) and cortisol in serum after generalised tonic-clonic or complex partial seizures has been one of the most consistent findings, although absences and myoclonic seizures, as well as seizures of very short duration, do not seem to affect PRL levels. The observation of a PRL increase in connection with epileptic seizures has been used as an aid in differentiating epileptic seizures from psychogenic attacks mimicking epileptic symptoms.

In our first study we hypothesised that PRL measurement could also be used to help classify different forms of status epilepticus (SE). However, we found no PRL increase during SE in 15 patients, irrespective of SE type and AED treatment. This finding was confirmed in an extended series of 32 patients with 34 episodes of SE, also as compared with control levels of PRL on a seizure-free day in 16 of the patients.

Cellular depletion of PRL due to long-standing epileptic activity was discussed as a possible mechanism behind the normal PRL levels in SE. We investigated PRL secretion in patients with SE in two studies by interfering with two different aspects of the PRL regulatory system. In the first, we administered metoclopramide, a dopamine receptor blocker, i.v. in connection with nine cases of SE, and in the second, thyrotropin-releasing hormone (TRH) i.v. in seven cases of SE. PRL levels increased in response to the injections in all cases. Thus we found no evidence for cellular depletion.

Since growth hormone (GH) and PRL partly share regulating substances, we decided also to study GH serum concentrations in connection with SE. GH levels were normal in 15 cases of SE, irrespective of type of SE and AED treatment.

To broaden our understanding of how epilepsy may affect the HPA, we studied patients with epilepsy under three different conditions: interictally during seizure-free periods (n=6), postictally immediately after a single seizure (n=6), and during SE (n=7). The responses of PRL, GH, cortisol, and TSH to TRH were investigated. PRL was elevated in the postictal group, with a further distinct increase after TRH administration. GH levels were normal in relation to seizure activity irrespective of seizure duration, whereas paradoxical GH responses to TRH were seen after both single seizures and SE. Cortisol levels were elevated after epileptic seizures, and this increase was maintained during SE. TSH reactivity to TRH seemed less pronounced in the SE group than in the postictal. Results in the interictal group were similar to those observed in healthy control subjects.

Our results demonstrate that both short- and long-standing epileptic seizure activity can alter pituitary hormone concentrations in serum, probably through influences on the regulation of the HPA. The hormonal changes seem related to the actual seizure activity, and not to the epilepsy disorder, nor to the metabolic condition of the patient or the AED treatment.

List of scientific papers

I. Tomson T, Lindbom U, Nilsson BY, Svanborg E, Andersson DE (1989). Serum prolactin during status epilepticus. J Neurol Neurosurg Psychiatry. 52(12): 1435-7.
https://pubmed.ncbi.nlm.nih.gov/90132741

II. Lindbom U, Tomson T, Nilsson BY, Andersson DE (1992). Serum prolactin response to metoclopramide during status epilepticus. J Neurol Neurosurg Psychiatry. 55(8): 685-7.
https://pubmed.ncbi.nlm.nih.gov/92407554

III. Lindbom U, Tomson T, Nilsson BY, Andersson DE (1993). Serum prolactin response to thyrotropin-releasing hormone during status epilepticus. Seizure. 2(3): 235-9.
https://pubmed.ncbi.nlm.nih.gov/94214940

IV. Lindbom U, Hulting AL, Tomson T (1999). Paradoxical GH response to TRH during status epilepticus in man. Eur J Endocrinol. 140(4): 307-14.
https://pubmed.ncbi.nlm.nih.gov/99208599

V. Lindbom U, Hulting AL, Bjellerup P, Tomson T (2000). Adeno-pituitary hormonal secretion in patients with epilepsy. [Submitted]